chr11-26441992-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_031418.4(ANO3):c.121G>A(p.Ala41Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A41P) has been classified as Uncertain significance.
Frequency
Consequence
NM_031418.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO3 | NM_031418.4 | c.121G>A | p.Ala41Thr | missense_variant | 2/27 | ENST00000256737.8 | |
ANO3 | NM_001313726.2 | c.304G>A | p.Ala102Thr | missense_variant | 3/28 | ||
ANO3 | XM_047427399.1 | c.121G>A | p.Ala41Thr | missense_variant | 2/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO3 | ENST00000256737.8 | c.121G>A | p.Ala41Thr | missense_variant | 2/27 | 1 | NM_031418.4 | P3 | |
ANO3 | ENST00000672621.1 | c.304G>A | p.Ala102Thr | missense_variant | 3/28 | ||||
ANO3 | ENST00000525139.5 | c.73G>A | p.Ala25Thr | missense_variant | 2/27 | 5 | |||
ANO3 | ENST00000531646.1 | c.121G>A | p.Ala41Thr | missense_variant | 2/5 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152002Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251428Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135884
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461816Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727214
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152002Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74220
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 2023 | The c.121G>A (p.A41T) alteration is located in exon 2 (coding exon 2) of the ANO3 gene. This alteration results from a G to A substitution at nucleotide position 121, causing the alanine (A) at amino acid position 41 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Dystonic disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 02, 2021 | This sequence change replaces alanine with threonine at codon 41 of the ANO3 protein (p.Ala41Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs150999282, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with ANO3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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