chr17-16353381-C-G

Variant names:

• chr17-16353381-C-G
• rs1182765383
• NM_181716.3:c.56G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_181716.3(CENPV):​c.56G>C​(p.Gly19Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,222,430 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000047 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: CENPV NM_181716.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00900
• Publications: 0 publications found

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]

ENSG00000307963 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.09039241).

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.56G>C	p.Gly19Ala	missense	Exon 1 of 5	NP_859067.2	Q7Z7K6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPV	ENST00000299736.5	TSL:1 MANE Select	c.56G>C	p.Gly19Ala	missense	Exon 1 of 5	ENSP00000299736.4	Q7Z7K6-3
	CENPV	ENST00000928025.1		c.56G>C	p.Gly19Ala	missense	Exon 1 of 5	ENSP00000598084.1
	CENPV	ENST00000476243.5	TSL:5	n.56G>C		non_coding_transcript_exon	Exon 1 of 5	ENSP00000462377.2	A0A0M3HER2

Frequencies

GnomAD3 genomes AF: 0.0000470 AC: 7 AN: 149056 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000172

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 2490 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: 0.0000140 AC: 15 AN: 1073268 Hom.: 0 Cov.: 37 AF XY: 0.00000778 AC XY: 4 AN XY: 514026

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

African (AFR) AF: 0.000284 AC: 6 AN: 21092

American (AMR) AF: 0.00 AC: 0 AN: 7494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12946

East Asian (EAS) AF: 0.000357 AC: 8 AN: 22434

South Asian (SAS) AF: 0.00 AC: 0 AN: 25280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2784

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 918244

Other (OTH) AF: 0.00 AC: 0 AN: 41694

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000382168), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000469 AC: 7 AN: 149162 Hom.: 0 Cov.: 33 AF XY: 0.0000274 AC XY: 2 AN XY: 72860

African (AFR) AF: 0.000172 AC: 7 AN: 40718

American (AMR) AF: 0.00 AC: 0 AN: 15044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5050

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67136

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.93
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.0090
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.024
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.28	B
Vest4		0.11
MutPred		0.22		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.067
MPC		1.2
ClinPred		0.17	T
GERP RS		0.66
PromoterAI		0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.091
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1182765383; hg19: chr17-16256695;