Variant 3-28435190-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000383768.7(ZCWPW2):c.413A>G(p.His138Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ZCWPW2
ENST00000383768.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.892

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZCWPW2	NM_001040432.4 linkuse as main transcript	c.413A>G	p.His138Arg	missense_variant	4/10	ENST00000383768.7	NP_001035522.1
ZCWPW2	NM_001324169.2 linkuse as main transcript	c.413A>G	p.His138Arg	missense_variant	3/9		NP_001311098.1
ZCWPW2	NM_001324170.2 linkuse as main transcript	c.413A>G	p.His138Arg	missense_variant	3/7		NP_001311099.1
ZCWPW2	NR_136708.2 linkuse as main transcript	n.909A>G		non_coding_transcript_exon_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZCWPW2	ENST00000383768.7 linkuse as main transcript	c.413A>G	p.His138Arg	missense_variant	4/10	1	NM_001040432.4	ENSP00000373278	P1
ZCWPW2	ENST00000428875.1 linkuse as main transcript	c.365A>G	p.His122Arg	missense_variant	2/4	5		ENSP00000393521
ZCWPW2	ENST00000419130.5 linkuse as main transcript			upstream_gene_variant		1		ENSP00000395687
ZCWPW2	ENST00000420223.5 linkuse as main transcript			downstream_gene_variant		5		ENSP00000395930

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461420

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727016

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:

0.0000108

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

Jan 09, 2024

The c.413A>G (p.H138R) alteration is located in exon 3 (coding exon 2) of the ZCWPW2 gene. This alteration results from a A to G substitution at nucleotide position 413, causing the histidine (H) at amino acid position 138 to be replaced by an arginine (R). 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

Pathogenic

0.75

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.71

M_CAP

Benign

0.029

MetaRNN

Pathogenic

0.89

MetaSVM

Uncertain

0.11

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.57

N;N

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.7

REVEL

Uncertain

0.58

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.018

Polyphen

1.0

Vest4

0.88

MutPred

0.62

Loss of disorder (P = 0.1357);

MVP

0.90

MPC

0.16

ClinPred

0.99

GERP RS

6.1

Varity_R

0.73

gMVP

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over