Variant 3-28435183-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001040432.4(ZCWPW2):c.406G>C(p.Glu136Gln) 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 1,461,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZCWPW2
NM_001040432.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.286

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056364536).

BP6

Variant 3-28435183-G-C is Benign according to our data. Variant chr3-28435183-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3192588.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZCWPW2	NM_001040432.4 linkuse as main transcript	c.406G>C	p.Glu136Gln	missense_variant	4/10	ENST00000383768.7	NP_001035522.1
ZCWPW2	NM_001324169.2 linkuse as main transcript	c.406G>C	p.Glu136Gln	missense_variant	3/9		NP_001311098.1
ZCWPW2	NM_001324170.2 linkuse as main transcript	c.406G>C	p.Glu136Gln	missense_variant	3/7		NP_001311099.1
ZCWPW2	NR_136708.2 linkuse as main transcript	n.902G>C		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.406G>C	p.Glu136Gln	missense_variant	4/10	1	NM_001040432.4	ENSP00000373278	P1
ZCWPW2	ENST00000428875.1 linkuse as main transcript	c.358G>C	p.Glu120Gln	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:

6.84e-7

AC:

AN:

1461426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.3

DANN

Benign

0.31

DEOGEN2

Benign

0.0024

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.55

M_CAP

Benign

0.0097

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.4

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.24

REVEL

Benign

0.12

Sift

Benign

0.78

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.14

MutPred

0.54

Loss of disorder (P = 0.1008);

MVP

0.33

MPC

0.019

ClinPred

0.033

GERP RS

-2.1

Varity_R

0.050

gMVP

0.29

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