Variant 3-28478831-T-G 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.510T>G(p.Asn170Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,551,138 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: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ZCWPW2
NM_001040432.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.50

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=0.015877217).

BP6

Variant 3-28478831-T-G is Benign according to our data. Variant chr3-28478831-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2471278.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.510T>G	p.Asn170Lys	missense_variant	5/10	ENST00000383768.7	NP_001035522.1
ZCWPW2	NM_001324169.2 linkuse as main transcript	c.510T>G	p.Asn170Lys	missense_variant	4/9		NP_001311098.1
ZCWPW2	NM_001324170.2 linkuse as main transcript	c.493-13296T>G		intron_variant			NP_001311099.1
ZCWPW2	NR_136708.2 linkuse as main transcript	n.989-13296T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCWPW2	ENST00000383768.7 linkuse as main transcript	c.510T>G	p.Asn170Lys	missense_variant	5/10	1	NM_001040432.4	ENSP00000373278	P1
ZCWPW2	ENST00000419130.5 linkuse as main transcript	c.165T>G	p.Asn55Lys	missense_variant	3/8	1		ENSP00000395687

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

214298

Hom.:

AF XY:

0.0000171

AC XY:

AN XY:

117076

show subpopulations

Gnomad AFR exome

AF:

0.000206

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000201

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1398976

Hom.:

Cov.:

AF XY:

0.00000864

AC XY:

AN XY:

694724

show subpopulations

Gnomad4 AFR exome

AF:

0.000262

Gnomad4 AMR exome

AF:

0.000122

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:

0.00

Gnomad4 OTH exome

AF:

0.0000347

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000992

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

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

Jan 24, 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

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.024

DANN

Benign

0.78

DEOGEN2

Benign

0.0082

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0081

LIST_S2

Benign

0.46

M_CAP

Benign

0.0055

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.035

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.6

REVEL

Benign

0.13

Sift

Benign

0.42

Sift4G

Benign

0.91

Polyphen

0.0

Vest4

0.058

MutPred

0.49

Gain of methylation at N170 (P = 0.0139);

MVP

0.030

MPC

0.019

ClinPred

0.015

GERP RS

-10

Varity_R

0.056

gMVP

0.082

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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