NM_007126.5:c.*1035delA

Variant names:

• chr9-35056081-GT-G
• rs532528005
• NM_007126.5:c.*1035delA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_007126.5(VCP):​c.*1035delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 144,440 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0027 (4 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: VCP NM_007126.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.839

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00271 (391/144440) while in subpopulation SAS AF= 0.0254 (116/4560). AF 95% confidence interval is 0.0217. There are 4 homozygotes in gnomad4. There are 231 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 391 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCP	NM_007126.5	c.*1035delA		3_prime_UTR_variant	Exon 17 of 17	ENST00000358901.11	NP_009057.1
VCP	NM_001354927.2	c.*1035delA		3_prime_UTR_variant	Exon 17 of 17		NP_001341856.1
VCP	NM_001354928.2	c.*1035delA		3_prime_UTR_variant	Exon 17 of 17		NP_001341857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCP	ENST00000358901	c.*1035delA		3_prime_UTR_variant	Exon 17 of 17	1	NM_007126.5	ENSP00000351777.6

Frequencies

GnomAD3 genomes AF: 0.00271 AC: 391 AN: 144392 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00577

Gnomad ASJ AF: 0.000299

Gnomad EAS AF: 0.00260

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.00148

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00201

Gnomad OTH AF: 0.00204

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.00271 AC: 391 AN: 144440 Hom.: 4 Cov.: 32 AF XY: 0.00330 AC XY: 231 AN XY: 69954

Gnomad4 AFR AF: 0.000732

Gnomad4 AMR AF: 0.00576

Gnomad4 ASJ AF: 0.000299

Gnomad4 EAS AF: 0.00261

Gnomad4 SAS AF: 0.0254

Gnomad4 FIN AF: 0.00148

Gnomad4 NFE AF: 0.00201

Gnomad4 OTH AF: 0.00202

Alfa AF: 0.000504 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs532528005; hg19: chr9-35056078;