rs777702397
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_014000.3(VCL):c.2887A>C(p.Asn963His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. N963D) has been classified as Uncertain significance.
Frequency
Consequence
NM_014000.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.2887A>C | p.Asn963His | missense_variant | 19/22 | ENST00000211998.10 | |
VCL | NM_003373.4 | c.2746-2134A>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.2887A>C | p.Asn963His | missense_variant | 19/22 | 1 | NM_014000.3 | ||
VCL | ENST00000372755.7 | c.2746-2134A>C | intron_variant | 1 | P1 | ||||
VCL | ENST00000623461.3 | n.5549-2134A>C | intron_variant, non_coding_transcript_variant | 1 | |||||
VCL | ENST00000624354.3 | c.*2642A>C | 3_prime_UTR_variant, NMD_transcript_variant | 18/21 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 35
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1W Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals with VCL-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with histidine at codon 963 of the VCL protein (p.Asn963His). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and histidine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.