Genetic Variant NM_181716.3:c.74C>T (chr17-16353363-G-A) – 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.74C>T(p.Ala25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000905 in 1,104,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A25G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

CENPV
NM_181716.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.01

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=0.065448076).

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.74C>T	p.Ala25Val	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.74C>T	p.Ala25Val	missense	Exon 1 of 5	ENSP00000299736.4	Q7Z7K6-3
CENPV	ENST00000928025.1		c.74C>T	p.Ala25Val	missense	Exon 1 of 5	ENSP00000598084.1
CENPV	ENST00000476243.5	TSL:5	n.74C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000462377.2	A0A0M3HER2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

8566

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.05e-7

AC:

AN:

1104400

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

533722

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22012

American (AMR)

AF:

0.00

AC:

AN:

9088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14304

East Asian (EAS)

AF:

0.0000419

AC:

AN:

23838

South Asian (SAS)

AF:

0.00

AC:

AN:

33258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2928

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

932170

Other (OTH)

AF:

0.00

AC:

AN:

43346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.0

(source)

DANN

Benign

0.96

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.51

M_CAP

Benign

0.083

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-2.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.18

REVEL

Benign

0.038

Sift

Benign

0.050

Sift4G

Uncertain

0.022

Polyphen

0.084

Vest4

0.035

MutPred

0.33

Loss of glycosylation at P24 (P = 0.0539)

MVP

0.067

MPC

1.1

ClinPred

0.12

GERP RS

-3.5

PromoterAI

-0.078

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

gMVP

0.089

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over