6-126340389-G-T

Position:

• chr6-126340389-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012507.4(CENPW):​c.116G>T​(p.Gly39Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CENPW NM_001012507.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.668

Genes affected

CENPW (HGNC:21488): (centromere protein W) Predicted to enable DNA binding activity and protein heterodimerization activity. Involved in chromosome segregation; kinetochore assembly; and mitotic cell cycle. Located in kinetochore and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CENPW (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0947454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPW	NM_001012507.4	c.116G>T	p.Gly39Val	missense_variant	1/3	ENST00000368328.5	NP_001012525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPW	ENST00000368328.5	c.116G>T	p.Gly39Val	missense_variant	1/3	1	NM_001012507.4	ENSP00000357311.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2024

The c.116G>T (p.G39V) alteration is located in exon 1 (coding exon 1) of the CENPW gene. This alteration results from a G to T substitution at nucleotide position 116, causing the glycine (G) at amino acid position 39 to be replaced by a valine (V). 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
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.0050	.;.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.2	D;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.021	D;T;T
Sift4G	Uncertain	0.021	D;T;T
Polyphen		0.0020	.;.;B
Vest4		0.35
MutPred		0.18		Loss of catalytic residue at G39 (P = 0.0098);Loss of catalytic residue at G39 (P = 0.0098);Loss of catalytic residue at G39 (P = 0.0098);
MVP		0.38
MPC		0.84
ClinPred		0.38	T
GERP RS		2.2
Varity_R		0.16
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-126661535;