rs375844934
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_024642.5(GALNT12):c.608A>G(p.Asn203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000819 in 1,612,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N203K) 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.608A>G | p.Asn203Ser | missense_variant | 3/10 | ENST00000375011.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALNT12 | ENST00000375011.4 | c.608A>G | p.Asn203Ser | missense_variant | 3/10 | 1 | NM_024642.5 | P1 | |
GALNT12 | ENST00000610463.1 | c.*39A>G | 3_prime_UTR_variant, NMD_transcript_variant | 2/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000109 AC: 27AN: 247990Hom.: 0 AF XY: 0.000119 AC XY: 16AN XY: 134210
GnomAD4 exome AF: 0.0000836 AC: 122AN: 1459926Hom.: 0 Cov.: 32 AF XY: 0.0000730 AC XY: 53AN XY: 726134
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74462
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 16, 2023 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 203 of the GALNT12 protein (p.Asn203Ser). This variant is present in population databases (rs375844934, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. 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: 410578). 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 not expected to disrupt GALNT12 protein function with a negative predictive value of 80%. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Aug 25, 2021 | - - |
Colorectal cancer, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 22, 2022 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 29, 2022 | The p.N203S variant (also known as c.608A>G), located in coding exon 3 of the GALNT12 gene, results from an A to G substitution at nucleotide position 608. The asparagine at codon 203 is replaced by serine, an amino acid with highly similar properties. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at