Variant chr3-28514093-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000383768.7(ZCWPW2):c.687G>C(p.Lys229Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000222 in 1,351,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.0000022 ( 0 hom. )

Consequence

ZCWPW2
ENST00000383768.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.810

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1206224).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZCWPW2	NM_001040432.4 linkuse as main transcript	c.687G>C	p.Lys229Asn	missense_variant	7/10	ENST00000383768.7	NP_001035522.1
ZCWPW2	NM_001324169.2 linkuse as main transcript	c.687G>C	p.Lys229Asn	missense_variant	6/9		NP_001311098.1
ZCWPW2	NM_001324170.2 linkuse as main transcript	c.569G>C	p.Arg190Thr	missense_variant	5/7		NP_001311099.1
ZCWPW2	NR_136708.2 linkuse as main transcript	n.1065G>C		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZCWPW2	ENST00000383768.7 linkuse as main transcript	c.687G>C	p.Lys229Asn	missense_variant	7/10	1	NM_001040432.4	ENSP00000373278	P1
ZCWPW2	ENST00000419130.5 linkuse as main transcript	c.342G>C	p.Lys114Asn	missense_variant	5/8	1		ENSP00000395687
ZCWPW2	ENST00000457897.1 linkuse as main transcript	c.156G>C	p.Lys52Asn	missense_variant	2/6	5		ENSP00000395421

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000222

AC:

AN:

1351572

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

669966

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:

0.00000291

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

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 07, 2024

The c.687G>C (p.K229N) alteration is located in exon 6 (coding exon 5) of the ZCWPW2 gene. This alteration results from a G to C substitution at nucleotide position 687, causing the lysine (K) at amino acid position 229 to be replaced by an asparagine (N). 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

0.17

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0063

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.44

M_CAP

Benign

0.012

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.5

REVEL

Benign

0.022

Sift

Benign

0.073

Sift4G

Uncertain

0.052

Polyphen

0.28

Vest4

0.37

MutPred

0.19

Loss of loop (P = 0.0203);

MVP

0.014

MPC

0.036

ClinPred

0.51

GERP RS

2.0

Varity_R

0.076

gMVP

0.072

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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