rs931730154
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1
The NM_001289808.2(CRYAB):c.134G>A(p.Ser45Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,246 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S45G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001289808.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYAB | NM_001289808.2 | c.134G>A | p.Ser45Asn | missense_variant | 1/3 | ENST00000650687.2 | |
CRYAB | NM_001289807.1 | c.134G>A | p.Ser45Asn | missense_variant | 2/4 | ||
CRYAB | NM_001368245.1 | c.134G>A | p.Ser45Asn | missense_variant | 2/4 | ||
CRYAB | NM_001885.3 | c.134G>A | p.Ser45Asn | missense_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYAB | ENST00000650687.2 | c.134G>A | p.Ser45Asn | missense_variant | 1/3 | NM_001289808.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249094Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134588
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461146Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 726762
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74282
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1II Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2022 | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 45 of the CRYAB protein (p.Ser45Asn). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 477731). 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. 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