8-66634778-T-G

Variant names:

• chr8-66634778-T-G
• NM_025054.5:c.3392A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025054.5(VCPIP1):​c.3392A>C​(p.Gln1131Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VCPIP1 NM_025054.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.69
• Publications: 0 publications found

Genes affected

VCPIP1 (HGNC:30897): (valosin containing protein interacting protein 1) Enables thiol-dependent deubiquitinase. Involved in protein deubiquitination; protein-DNA covalent cross-linking repair; and regulation of protein localization to chromatin. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20359623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCPIP1	NM_025054.5	c.3392A>C	p.Gln1131Pro	missense_variant	Exon 3 of 3	ENST00000310421.5	NP_079330.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCPIP1	ENST00000310421.5	c.3392A>C	p.Gln1131Pro	missense_variant	Exon 3 of 3	1	NM_025054.5	ENSP00000309031.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3392A>C (p.Q1131P) alteration is located in exon 3 (coding exon 3) of the VCPIP1 gene. This alteration results from a A to C substitution at nucleotide position 3392, causing the glutamine (Q) at amino acid position 1131 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	L
PhyloP100		6.7
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.019	D
Polyphen		0.87	P
Vest4		0.41
MutPred		0.060		Gain of relative solvent accessibility (P = 0.0275);
MVP		0.11
MPC		0.90
ClinPred		0.69	D
GERP RS		5.6
Varity_R		0.17
gMVP		0.36
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr8-67547013;