8-66635055-G-T

Position:

• chr8-66635055-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025054.5(VCPIP1):​c.3115C>A​(p.Pro1039Thr) 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. 14/21 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: 4.01

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06924355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCPIP1	NM_025054.5	c.3115C>A	p.Pro1039Thr	missense_variant	3/3	ENST00000310421.5	NP_079330.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCPIP1	ENST00000310421.5	c.3115C>A	p.Pro1039Thr	missense_variant	3/3	1	NM_025054.5	ENSP00000309031	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.3115C>A (p.P1039T) alteration is located in exon 3 (coding exon 3) of the VCPIP1 gene. This alteration results from a C to A substitution at nucleotide position 3115, causing the proline (P) at amino acid position 1039 to be replaced by a threonine (T). 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	0.061
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	0.98	D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.045
Sift	Uncertain	0.028	D
Sift4G	Benign	0.085	T
Polyphen		0.26	B
Vest4		0.033
MutPred		0.19		Loss of stability (P = 0.05);
MVP		0.068
MPC		0.73
ClinPred		0.20	T
GERP RS		3.3
Varity_R		0.042
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-67547290;