chr5-83483532-T-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_004385.5(VCAN):āc.14T>Cā(p.Ile5Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,374 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_004385.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VCAN | NM_004385.5 | c.14T>C | p.Ile5Thr | missense_variant | Exon 2 of 15 | ENST00000265077.8 | NP_004376.2 | |
VCAN | NM_001164097.2 | c.14T>C | p.Ile5Thr | missense_variant | Exon 2 of 14 | NP_001157569.1 | ||
VCAN | NM_001164098.2 | c.14T>C | p.Ile5Thr | missense_variant | Exon 2 of 14 | NP_001157570.1 | ||
VCAN | NM_001126336.3 | c.14T>C | p.Ile5Thr | missense_variant | Exon 2 of 13 | NP_001119808.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251116Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135720
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461172Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 726904
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 5 of the VCAN protein (p.Ile5Thr). This variant is present in population databases (rs766706928, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with VCAN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1510137). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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