17-16348639-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_181716.3(CENPV):​c.556G>C​(p.Ala186Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CENPV
NM_181716.3 missense

Scores

1
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.84
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]
PIGL (HGNC:8966): (phosphatidylinositol glycan anchor biosynthesis class L) This gene encodes an enzyme that catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which is the de-N-acetylation of N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI). Study of a similar rat enzyme suggests that this protein localizes to the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CENPVNM_181716.3 linkc.556G>C p.Ala186Pro missense_variant Exon 3 of 5 ENST00000299736.5 NP_859067.2 Q7Z7K6-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CENPVENST00000299736.5 linkc.556G>C p.Ala186Pro missense_variant Exon 3 of 5 1 NM_181716.3 ENSP00000299736.4 Q7Z7K6-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.556G>C (p.A186P) alteration is located in exon 3 (coding exon 3) of the CENPV gene. This alteration results from a G to C substitution at nucleotide position 556, causing the alanine (A) at amino acid position 186 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
25
DANN
Benign
0.95
Eigen
Benign
0.018
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.0035
T
MetaRNN
Uncertain
0.52
D
MetaSVM
Benign
-0.94
T
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-3.5
D
REVEL
Benign
0.14
Sift
Benign
0.097
T
Sift4G
Benign
0.097
T
Polyphen
0.34
B
Vest4
0.68
MutPred
0.65
Loss of MoRF binding (P = 0.055);
MVP
0.36
MPC
1.5
ClinPred
0.68
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-16251953; API