chr9-35061172-T-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BS1BS2
The NM_007126.5(VCP):c.1202A>G(p.Asn401Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,613,282 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N401I) has been classified as Uncertain significance.
Frequency
Consequence
NM_007126.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCP | NM_007126.5 | c.1202A>G | p.Asn401Ser | missense_variant | 11/17 | ENST00000358901.11 | |
VCP | NM_001354927.2 | c.1067A>G | p.Asn356Ser | missense_variant | 11/17 | ||
VCP | NM_001354928.2 | c.1067A>G | p.Asn356Ser | missense_variant | 11/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCP | ENST00000358901.11 | c.1202A>G | p.Asn401Ser | missense_variant | 11/17 | 1 | NM_007126.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000346 AC: 87AN: 251264Hom.: 0 AF XY: 0.000464 AC XY: 63AN XY: 135792
GnomAD4 exome AF: 0.000170 AC: 248AN: 1460984Hom.: 1 Cov.: 36 AF XY: 0.000242 AC XY: 176AN XY: 726814
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74486
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 19, 2021 | This variant is associated with the following publications: (PMID: 27990419, 32403337, 27439681) - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 18, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 30, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
VCP-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 24, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia;C5436279:Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at