chr8-66664449-G-C

Variant summary

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

The NM_025054.5(VCPIP1):ā€‹c.2510C>Gā€‹(p.Pro837Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,504 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

VCPIP1
NM_025054.5 missense

Scores

5
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.56
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VCPIP1NM_025054.5 linkuse as main transcriptc.2510C>G p.Pro837Arg missense_variant 1/3 ENST00000310421.5 NP_079330.2 Q96JH7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VCPIP1ENST00000310421.5 linkuse as main transcriptc.2510C>G p.Pro837Arg missense_variant 1/31 NM_025054.5 ENSP00000309031.4 Q96JH7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461504
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727012
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 17, 2021The c.2510C>G (p.P837R) alteration is located in exon 1 (coding exon 1) of the VCPIP1 gene. This alteration results from a C to G substitution at nucleotide position 2510, causing the proline (P) at amino acid position 837 to be replaced by an arginine (R). 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
Uncertain
0.53
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.084
T
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.033
D
MetaRNN
Uncertain
0.63
D
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-2.6
D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0060
D
Polyphen
1.0
D
Vest4
0.81
MutPred
0.28
Loss of loop (P = 0.0203);
MVP
0.33
MPC
1.7
ClinPred
0.98
D
GERP RS
5.5
Varity_R
0.54
gMVP
0.48

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: chr8-67576684; API