Variant 3-28521010-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000383768.7(ZCWPW2):c.803T>C(p.Val268Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZCWPW2
ENST00000383768.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.223

Variant links:

Genes affected

ZCWPW2 (HGNC:23574): (zinc finger CW-type and PWWP domain containing 2) Enables methylated histone binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZCWPW2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03443715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZCWPW2	NM_001040432.4 linkuse as main transcript	c.803T>C	p.Val268Ala	missense_variant	9/10	ENST00000383768.7	NP_001035522.1
ZCWPW2	NM_001324169.2 linkuse as main transcript	c.803T>C	p.Val268Ala	missense_variant	8/9		NP_001311098.1
ZCWPW2	NM_001324170.2 linkuse as main transcript	c.617T>C	p.Val206Ala	missense_variant	6/7		NP_001311099.1
ZCWPW2	NR_136708.2 linkuse as main transcript	n.1181T>C		non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZCWPW2	ENST00000383768.7 linkuse as main transcript	c.803T>C	p.Val268Ala	missense_variant	9/10	1	NM_001040432.4	ENSP00000373278	P1
ZCWPW2	ENST00000419130.5 linkuse as main transcript	c.458T>C	p.Val153Ala	missense_variant	7/8	1		ENSP00000395687
ZCWPW2	ENST00000457897.1 linkuse as main transcript	c.272T>C	p.Val91Ala	missense_variant	4/6	5		ENSP00000395421

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.803T>C (p.V268A) alteration is located in exon 8 (coding exon 7) of the ZCWPW2 gene. This alteration results from a T to C substitution at nucleotide position 803, causing the valine (V) at amino acid position 268 to be replaced by an alanine (A). 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

0.16

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0087

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.36

M_CAP

Benign

0.0055

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.060

REVEL

Benign

0.019

Sift

Uncertain

0.028

Sift4G

Benign

0.16

Polyphen

0.0080

Vest4

0.11

MutPred

0.23

Gain of disorder (P = 0.05);

MVP

0.18

MPC

0.021

ClinPred

0.18

GERP RS

0.30

Varity_R

0.048

gMVP

0.067

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over