rs727503742
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_014000.3(VCL):āc.3236T>Cā(p.Ile1079Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,448,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. I1079I) has been classified as Likely benign.
Frequency
Consequence
NM_014000.3 missense
Scores
Clinical Significance
Conservation
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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.3236T>C | p.Ile1079Thr | missense_variant | 21/22 | ENST00000211998.10 | |
VCL | NM_003373.4 | c.3032T>C | p.Ile1011Thr | missense_variant | 20/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.3236T>C | p.Ile1079Thr | missense_variant | 21/22 | 1 | NM_014000.3 | ||
VCL | ENST00000372755.7 | c.3032T>C | p.Ile1011Thr | missense_variant | 20/21 | 1 | P1 | ||
VCL | ENST00000623461.3 | n.5835T>C | non_coding_transcript_exon_variant | 22/23 | 1 | ||||
VCL | ENST00000624354.3 | c.*2991T>C | 3_prime_UTR_variant, NMD_transcript_variant | 20/21 | 2 |
Frequencies
GnomAD3 genomes Cov.: 29
GnomAD4 exome AF: 0.00000276 AC: 4AN: 1448828Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1AN XY: 719360
GnomAD4 genome Cov.: 29
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 | Aug 11, 2014 | The Ile1079Thr variant in VCL has not been previously reported in individuals wi th cardiomyopathy or in large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impac t to the protein. In summary, the clinical significance of the Ile1079Thr varian t is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at