Genetic Variant CENPV:p.Glu54Lys (chr17-16353277-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181716.3(CENPV):c.160G>A(p.Glu54Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,421,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

CENPV
NM_181716.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.01

Publications

0 publications found

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:

ENSG00000307963 (HGNC:):

ENSG00000307963 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05166903).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181716.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPV	NM_181716.3	MANE Select	c.160G>A	p.Glu54Lys	missense	Exon 1 of 5	NP_859067.2	Q7Z7K6-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CENPV	ENST00000299736.5	TSL:1 MANE Select	c.160G>A	p.Glu54Lys	missense	Exon 1 of 5	ENSP00000299736.4	Q7Z7K6-3
CENPV	ENST00000928025.1		c.160G>A	p.Glu54Lys	missense	Exon 1 of 5	ENSP00000598084.1
CENPV	ENST00000476243.5	TSL:5	n.160G>A		non_coding_transcript_exon	Exon 1 of 5	ENSP00000462377.2	A0A0M3HER2

Frequencies

GnomAD3 genomes

AF:

0.0000792

AC:

AN:

151538

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000422

AC:

AN:

71164

AF XY:

0.0000483

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000755

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1269932

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

625282

show subpopulations

African (AFR)

AF:

0.000116

AC:

AN:

25948

American (AMR)

AF:

0.00

AC:

AN:

23210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21880

East Asian (EAS)

AF:

0.00

AC:

AN:

26650

South Asian (SAS)

AF:

0.0000916

AC:

AN:

65484

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3664

European-Non Finnish (NFE)

AF:

0.0000265

AC:

AN:

1020120

Other (OTH)

AF:

0.0000773

AC:

AN:

51742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000791

AC:

AN:

151644

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74144

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67846

Other (OTH)

AF:

0.00

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000152

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.6

(source)

DANN

Benign

0.92

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.39

M_CAP

Benign

0.019

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

PhyloP100

-1.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.040

REVEL

Benign

0.071

Sift

Benign

0.066

Sift4G

Benign

0.10

Polyphen

0.0

Vest4

0.089

MutPred

0.27

Gain of methylation at E54 (P = 0.0053)

MVP

0.076

MPC

1.2

ClinPred

0.042

GERP RS

-2.0

PromoterAI

-0.0042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

gMVP

0.12

Mutation Taster

=299/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over