rs1439506011
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_024642.5(GALNT12):c.214G>T(p.Ala72Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,212,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A72G) has been classified as Uncertain significance.
Frequency
Consequence
NM_024642.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALNT12 | NM_024642.5 | c.214G>T | p.Ala72Ser | missense_variant | 1/10 | ENST00000375011.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALNT12 | ENST00000375011.4 | c.214G>T | p.Ala72Ser | missense_variant | 1/10 | 1 | NM_024642.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000534 AC: 8AN: 149754Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.000127 AC: 135AN: 1062418Hom.: 0 Cov.: 30 AF XY: 0.000145 AC XY: 73AN XY: 502848
GnomAD4 genome ? AF: 0.0000534 AC: 8AN: 149754Hom.: 0 Cov.: 32 AF XY: 0.0000410 AC XY: 3AN XY: 73108
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 31, 2023 | The p.A72S variant (also known as c.214G>T), located in coding exon 1 of the GALNT12 gene, results from a G to T substitution at nucleotide position 214. The alanine at codon 72 is replaced by serine, an amino acid with similar properties. The p.A72S alteration was identified in a cohort of 110 families with colon neoplasia undergoing linkage analysis, but functional consequence of this variant was not assessed (Gray-McGuire C et al. Cancer Res. 2010 Jul;70:5409-18). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 05, 2022 | This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 72 of the GALNT12 protein (p.Ala72Ser). This variant has not been reported in the literature in individuals affected with GALNT12-related conditions. ClinVar contains an entry for this variant (Variation ID: 485647). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at