Genetic Variant CENPV:p.Ser6Thr (chr17-16353420-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181716.3(CENPV):c.17G>C(p.Ser6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,167,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. S6R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000020 ( 0 hom. )

Consequence

CENPV
NM_181716.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.153

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07424569).

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.17G>C	p.Ser6Thr	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.17G>C	p.Ser6Thr	missense	Exon 1 of 5	ENSP00000299736.4	Q7Z7K6-3
CENPV	ENST00000928025.1		c.17G>C	p.Ser6Thr	missense	Exon 1 of 5	ENSP00000598084.1
CENPV	ENST00000476243.5	TSL:5	n.17G>C		non_coding_transcript_exon	Exon 1 of 5	ENSP00000462377.2	A0A0M3HER2

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

148406

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000669

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000196

AC:

AN:

1019058

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

481024

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

20428

American (AMR)

AF:

0.00

AC:

AN:

6240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11470

East Asian (EAS)

AF:

0.00

AC:

AN:

19664

South Asian (SAS)

AF:

0.00

AC:

AN:

19518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2554

European-Non Finnish (NFE)

AF:

0.00000227

AC:

AN:

881932

Other (OTH)

AF:

0.00

AC:

AN:

38874

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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:

0.0000135

AC:

AN:

148406

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40964

American (AMR)

AF:

0.0000669

AC:

AN:

14946

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

5066

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66674

Other (OTH)

AF:

0.00

AC:

AN:

2044

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

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.94

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.35

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.15

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.21

REVEL

Benign

0.034

Sift

Uncertain

0.0070

Sift4G

Benign

0.53

Polyphen

0.072

Vest4

0.10

MutPred

0.12

Gain of glycosylation at S4 (P = 0.1232)

MVP

0.067

MPC

0.99

ClinPred

0.18

GERP RS

1.6

PromoterAI

-0.074

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.086

Mutation Taster

=94/6

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