rs774573497
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004281.4(BAG3):c.1623T>A(p.Asn541Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,894 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 (★).
Frequency
Consequence
NM_004281.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251286Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135822
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461820Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727198
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74270
ClinVar
Submissions by phenotype
Myofibrillar myopathy 6;C3151293:Dilated cardiomyopathy 1HH Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 26, 2020 | 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BAG3-related disease. ClinVar contains an entry for this variant (Variation ID: 410234). This variant is present in population databases (rs774573497, ExAC 0.002%). This sequence change replaces asparagine with lysine at codon 541 of the BAG3 protein (p.Asn541Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at