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GALNT12
Final classification
VUS
GALNT12 c.-28C>T · p.?
GALNT12

NM_024642.5:c.-28C>T is a 5' UTR variant in GALNT12. It is present at extremely low frequency in gnomAD (v2.1 AF=0.00327%, v4.1 AF=0.00435%), meeting PM2 at supporting level.

Gene
GALNT12
Transcript
NM_024642.5
HGVS · transcript:coding
NM_024642.5:c.-28C>T
Consequence
N/A
GRCh38
chr9:98807671 C>T
GRCh37
chr9:101569953 C>T
Basis gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting; combination = 1 supporting, which maps to VUS.
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting; combination = 1 supporting, which maps to VUS.
Classification rationale
PM2 VUS
GALNT12 c.-28C>T

NM_024642.5:c.-28C>T is a 5' UTR variant in GALNT12. It is present at extremely low frequency in gnomAD (v2.1 AF=0.00327%, v4.1 AF=0.00435%), meeting PM2 at supporting level.1 SpliceAI predicts no splicing impact (max delta score = 0.00), but this single line of computational evidence is insufficient to meet PP3 or BP4 thresholds. REVEL and BayesDel scores are unavailable as the variant does not alter an amino acid.2 This variant is absent from ClinVar and has not been reported in the published literature. No functional studies, case-control data, cosegregation data, or de novo observations are available.3 PVS1 is not applicable as c.-28C>T is a 5' UTR substitution rather than a null variant (nonsense, frameshift, canonical splice, initiation codon, or exon deletion) eligible under the ClinGen SVI framework.4 BS2 is not applicable for this gene: GALNT12 is a moderate-penetrance adult-onset cancer predisposition gene, and observation in healthy population controls does not constitute strong evidence against pathogenicity. The only criterion met is PM2 (supporting). All other assessed criteria are either not met, not assessed due to insufficient evidence, or not applicable. This yields a classification of Variant of Uncertain Significance (VUS) per ACMG/AMP 2015 generic rules.5

PM2 VUS
Gene diagram · NM_024642.5 · variants mapped to exon structure
GALNT12 NM_024642.5
Fetching transcript structure from UCSC…
Applied criteria · 1 met · select any tile
Met
Not met
Not assessed
N/A
Strength very strong supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
Rationale
Select a criterion.
Sources
Evidence used
    Gaps remaining
      Rule
      Research & evidence
      Population frequency
      gnomAD v4.1 screenshot
      gnomAD v4.1
      gnomAD v2.1 screenshot
      gnomAD v2.1
      Population frequency
      Overall AF
      48 / 1,104,678
      0.0043%
      Highest · European (non-Finnish)
      0.0052%
      Homozygotes
      0
      grpmax FAF
      0.004%
      Allele frequency by ancestry — gnomAD v4.1
      observed in 1 of 9 groups
      AncestryAllele countFrequencyHomozygotes
      European (non-Finnish) 47 / 908,646 0.0052% 0
      Admixed American 0 / 19,222
      European (Finnish) 0 / 21,498
      Amish 0 / 906
      East Asian 0 / 18,218
      Middle Eastern 0 / 2,518
      South Asian 0 / 25,542
      Ashkenazi Jewish 0 / 12,132
      African/African American 0 / 59,718
      This variant is present in gnomAD v4.1 (AF= 4.34516e-05; MAF= 0.00435%, 48/1104678 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 5.17253e-05; MAF= 0.00517%, 47/908646 alleles, homozygotes = 0); grpmax FAF= 3.985e-05.
      Overall AF
      1 / 30,612
      0.0033%
      Highest · European (non-Finnish)
      0.0065%
      Homozygotes
      0
      Allele frequency by ancestry — gnomAD v2.1
      observed in 1 of 8 groups
      AncestryAllele countFrequencyHomozygotes
      European (non-Finnish) 1 / 15,334 0.0065% 0
      African/African American 0 / 8,558
      Admixed American 0 / 810
      Ashkenazi Jewish 0 / 310
      East Asian 0 / 1,556
      European (Finnish) 0 / 2,900
      Remaining individuals 0 / 1,040
      South Asian 0 / 104
      This variant is present in gnomAD v2.1 (AF= 3.26669e-05; MAF= 0.00327%, 1/30612 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.52146e-05; MAF= 0.00652%, 1/15334 alleles, homozygotes = 0).
      This variant is absent from gnomAD-Canada.
      ClinVar screenshot
      ClinVar
      This variant is absent from ClinVar.
      SpliceAI screenshot
      In silico
      SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
      Functional No data
      No calibrated functional assay or RNA evidence was identified for this variant.
      OncoKB ↗
      COSMIC screenshot
      COSMIC
      Somatic evidence
      COSMIC
      This variant has not previously been reported in somatic cancers (COSMIC).
      Hotspots
      This variant does not lie in a statistically significant cancer hotspot.
      COSMIC ↗
      Sources & reference links
      6Sources
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      SpliceAI
      OncoKB
      COSMIC