12-65278841-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000355192.8(MSRB3):c.73G>A(p.Ala25Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. A25S) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000355192.8 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MSRB3 | NM_001031679.3 | c.-76G>A | 5_prime_UTR_variant | 1/7 | ENST00000308259.10 | NP_001026849.1 | ||
MSRB3 | NM_198080.4 | c.73G>A | p.Ala25Thr | missense_variant | 1/6 | NP_932346.1 | ||
MSRB3 | NM_001193460.2 | c.-240G>A | 5_prime_UTR_variant | 1/8 | NP_001180389.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MSRB3 | ENST00000308259.10 | c.-76G>A | 5_prime_UTR_variant | 1/7 | 1 | NM_001031679.3 | ENSP00000312274 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 7.08e-7 AC: 1AN: 1412182Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1AN XY: 697658
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 04, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with MSRB3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 25 of the MSRB3 protein (p.Ala25Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at