chr10-80157676-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_145868.2(ANXA11):c.1423C>T(p.Arg475Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,613,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R475Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_145868.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANXA11 | NM_145868.2 | c.1423C>T | p.Arg475Trp | missense_variant | 15/16 | ENST00000422982.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANXA11 | ENST00000422982.8 | c.1423C>T | p.Arg475Trp | missense_variant | 15/16 | 1 | NM_145868.2 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000790 AC: 12AN: 151972Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251290Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135804
GnomAD4 exome AF: 0.000140 AC: 205AN: 1461790Hom.: 0 Cov.: 32 AF XY: 0.000140 AC XY: 102AN XY: 727210
GnomAD4 genome AF: 0.0000855 AC: 13AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74334
ClinVar
Submissions by phenotype
ANXA11-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 13, 2024 | The ANXA11 c.1423C>T variant is predicted to result in the amino acid substitution p.Arg475Trp. This variant was reported in a study of individuals with a definite or probable diagnosis of amyotrophic lateral sclerosis (ALS) (Jiang et al. 2022. PubMed ID: 36280108). This variant is reported in 0.013% of alleles in individuals of South Asian descent in gnomAD, which may be too common to be a primary cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 26, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 475 of the ANXA11 protein (p.Arg475Trp). This variant is present in population databases (rs368132715, gnomAD 0.01%). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 36280108). ClinVar contains an entry for this variant (Variation ID: 1352634). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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