chr10-80157675-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting
The NM_145868.2(ANXA11):c.1424G>A(p.Arg475Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R475W) 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.1424G>A | p.Arg475Gln | missense_variant | 15/16 | ENST00000422982.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANXA11 | ENST00000422982.8 | c.1424G>A | p.Arg475Gln | missense_variant | 15/16 | 1 | NM_145868.2 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152032Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251284Hom.: 0 AF XY: 0.0000884 AC XY: 12AN XY: 135802
GnomAD4 exome AF: 0.0000547 AC: 80AN: 1461770Hom.: 0 Cov.: 32 AF XY: 0.0000633 AC XY: 46AN XY: 727196
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 03, 2023 | 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 1398399). This variant has not been reported in the literature in individuals affected with ANXA11-related conditions. This variant is present in population databases (rs146644733, gnomAD 0.04%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 475 of the ANXA11 protein (p.Arg475Gln). - |
Amyotrophic lateral sclerosis type 23 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Zotz-Klimas Genetics Lab, MVZ Zotz Klimas | Nov 02, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at