GeneBe

NM_007126.5:c.1194+15_1194+17dupATG

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007126.5(VCP):​c.1194+15_1194+17dupATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,194 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

VCP
NM_007126.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.221

Publications

0 publications found
Variant links:
Genes affected
VCP (HGNC:12666): (valosin containing protein) This gene encodes a member of the AAA ATPase family of proteins. The encoded protein plays a role in protein degradation, intracellular membrane fusion, DNA repair and replication, regulation of the cell cycle, and activation of the NF-kappa B pathway. This protein forms a homohexameric complex that interacts with a variety of cofactors and extracts ubiquitinated proteins from lipid membranes or protein complexes. Mutations in this gene cause IBMPFD (inclusion body myopathy with paget disease of bone and frontotemporal dementia), ALS (amyotrophic lateral sclerosis) and Charcot-Marie-Tooth disease in human patients. [provided by RefSeq, Aug 2017]
VCP Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
  • inclusion body myopathy with Paget disease of bone and frontotemporal dementia
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
  • Charcot-Marie-Tooth disease type 2Y
    Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
  • frontotemporal dementia and/or amyotrophic lateral sclerosis 6
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
  • inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • adult-onset distal myopathy due to VCP mutation
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • amyotrophic lateral sclerosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • frontotemporal dementia with motor neuron disease
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • spastic paraplegia-Paget disease of bone syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • neurodevelopmental disorder
    Inheritance: AD Classification: LIMITED Submitted by: G2P

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VCPNM_007126.5 linkc.1194+15_1194+17dupATG intron_variant Intron 10 of 16 ENST00000358901.11 NP_009057.1
VCPNM_001354927.2 linkc.1059+15_1059+17dupATG intron_variant Intron 10 of 16 NP_001341856.1
VCPNM_001354928.2 linkc.1059+15_1059+17dupATG intron_variant Intron 10 of 16 NP_001341857.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VCPENST00000358901.11 linkc.1194+15_1194+17dupATG intron_variant Intron 10 of 16 1 NM_007126.5 ENSP00000351777.6 P55072

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457194
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725240
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33368
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26104
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39662
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86164
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
9.03e-7
AC:
1
AN:
1107748
Other (OTH)
AF:
0.00
AC:
0
AN:
60258
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs886038581; hg19: chr9-35061556; API