rs868590153
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_024642.5(GALNT12):c.1145G>A(p.Arg382His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R382C) has been classified as Uncertain significance.
Frequency
Consequence
NM_024642.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALNT12 | NM_024642.5 | c.1145G>A | p.Arg382His | missense_variant | 6/10 | ENST00000375011.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALNT12 | ENST00000375011.4 | c.1145G>A | p.Arg382His | missense_variant | 6/10 | 1 | NM_024642.5 | P1 | |
GALNT12 | ENST00000615204.1 | n.7G>A | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251486Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135920
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.0000234 AC XY: 17AN XY: 727248
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74334
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 21, 2023 | The p.R382H variant (also known as c.1145G>A), located in coding exon 6 of the GALNT12 gene, results from a G to A substitution at nucleotide position 1145. The arginine at codon 382 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. - |
Colorectal cancer, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 30, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 18, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 382 of the GALNT12 protein (p.Arg382His). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with colon cancer (PMID: 19617566). ClinVar contains an entry for this variant (Variation ID: 485662). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GALNT12 protein function. Experimental studies have shown that this missense change affects GALNT12 function (PMID: 19617566). 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