Genetic Variant CENPV:p.Arg13His (chr17-16353399-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181716.3(CENPV):c.38G>A(p.Arg13His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000766 in 1,043,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

CENPV
NM_181716.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.926

Variant links:

Genes affected

CENPV (HGNC:29920): (centromere protein V) Predicted to enable carbon-sulfur lyase activity and metal ion binding activity. Involved in pericentric heterochromatin assembly; positive regulation of cytokinesis; and regulation of chromosome organization. Acts upstream of or within ameboidal-type cell migration. Located in several cellular components, including midbody; nucleus; and spindle midzone. [provided by Alliance of Genome Resources, Apr 2022]

CENPV links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10374385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPV	NM_181716.3 link	c.38G>A	p.Arg13His	missense_variant	Exon 1 of 5	ENST00000299736.5	NP_859067.2	Q7Z7K6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPV	ENST00000299736.5 link	c.38G>A	p.Arg13His	missense_variant	Exon 1 of 5	1	NM_181716.3	ENSP00000299736.4		Q7Z7K6-3

Frequencies

GnomAD3 genomes

AF:

0.0000142

AC:

AN:

140446

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000700

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000664

AC:

AN:

903320

Hom.:

Cov.:

AF XY:

0.00000468

AC XY:

AN XY:

427604

show subpopulations

Gnomad4 AFR exome

AF:

0.0000539

Gnomad4 AMR exome

AF:

0.000174

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:

0.00000255

Gnomad4 OTH exome

AF:

0.0000581

GnomAD4 genome

AF:

0.0000142

AC:

AN:

140446

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

68326

show subpopulations

Gnomad4 AFR

AF:

0.0000258

Gnomad4 AMR

AF:

0.0000700

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000680

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.38G>A (p.R13H) alteration is located in exon 1 (coding exon 1) of the CENPV gene. This alteration results from a G to A substitution at nucleotide position 38, causing the arginine (R) at amino acid position 13 to be replaced by a histidine (H). 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

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.63

REVEL

Benign

0.018

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0080

Polyphen

0.0090

Vest4

0.042

MutPred

0.29

Loss of methylation at R13 (P = 0.0321);

MVP

0.061

MPC

1.3

ClinPred

0.22

GERP RS

-0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over