chr17-16353420-C-A

Variant names:

• chr17-16353420-C-A
• rs1248685432
• NM_181716.3:c.17G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181716.3(CENPV):​c.17G>T​(p.Ser6Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000514 in 1,167,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: CENPV NM_181716.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.153
• 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: 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=0.11444563).

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>T	p.Ser6Ile	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.17G>T	p.Ser6Ile	missense	Exon 1 of 5	ENSP00000299736.4	Q7Z7K6-3
	CENPV	ENST00000928025.1		c.17G>T	p.Ser6Ile	missense	Exon 1 of 5	ENSP00000598084.1
	CENPV	ENST00000476243.5	TSL:5	n.17G>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000462377.2	A0A0M3HER2

Frequencies

GnomAD3 genomes AF: 0.00000674 AC: 1 AN: 148406 Hom.: 0 Cov.: 32

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000491 AC: 5 AN: 1019058 Hom.: 0 Cov.: 33 AF XY: 0.00000208 AC XY: 1 AN XY: 481024

African (AFR) AF: 0.00 AC: 0 AN: 20428

American (AMR) AF: 0.00 AC: 0 AN: 6240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11470

East Asian (EAS) AF: 0.00 AC: 0 AN: 19664

South Asian (SAS) AF: 0.00 AC: 0 AN: 19518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2554

European-Non Finnish (NFE) AF: 0.00000567 AC: 5 AN: 881932

Other (OTH) AF: 0.00 AC: 0 AN: 38874

GnomAD4 genome AF: 0.00000674 AC: 1 AN: 148406 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72350

African (AFR) AF: 0.00 AC: 0 AN: 40964

American (AMR) AF: 0.0000669 AC: 1 AN: 14946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 5066

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66674

Other (OTH) AF: 0.00 AC: 0 AN: 2044

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Uncertain	0.37
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.97
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.44	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.15
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.047
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.059	T
Polyphen		0.57	P
Vest4		0.13
MutPred		0.23		Loss of phosphorylation at S6 (P = 0.0012)
MVP		0.17
MPC		1.3
ClinPred		0.45	T
GERP RS		1.6
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.19
Mutation Taster		=97/3	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: rs1248685432; hg19: chr17-16256734;