rs727503740
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_014000.3(VCL):c.2672G>C(p.Gly891Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 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. G891R) has been classified as Uncertain significance.
Frequency
Consequence
NM_014000.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.2672G>C | p.Gly891Ala | missense_variant | 18/22 | ENST00000211998.10 | |
VCL | NM_003373.4 | c.2672G>C | p.Gly891Ala | missense_variant | 18/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.2672G>C | p.Gly891Ala | missense_variant | 18/22 | 1 | NM_014000.3 | ||
VCL | ENST00000372755.7 | c.2672G>C | p.Gly891Ala | missense_variant | 18/21 | 1 | P1 | ||
VCL | ENST00000623461.3 | n.5475G>C | non_coding_transcript_exon_variant | 20/23 | 1 | ||||
VCL | ENST00000624354.3 | c.*2427G>C | 3_prime_UTR_variant, NMD_transcript_variant | 17/21 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727236
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 26, 2013 | The Gly891Ala variant in VCL has not been reported in individuals with cardiomyo pathy or in large population studies. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide st rong support for or against an impact to the protein. At this time, additional i nformation is needed to fully assess the clinical significance of this variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at