Variant X-64917866-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_018684.4(ZC4H2):c.592C>A(p.Arg198Arg) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00022 in 1,208,193 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 66 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., 38 hem., cov: 22)

Exomes 𝑓: 0.00012 ( 0 hom. 28 hem. )

Consequence

ZC4H2
NM_018684.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 9.22

Variant links:

Genes affected

ZC4H2 (HGNC:24931): (zinc finger C4H2-type containing) This gene encodes a member of the zinc finger domain-containing protein family. This family member has a C-terminal zinc finger domain that is characterized by four cysteine residues and two histidine residues, and it also includes a coiled-coil region. This protein has been detected as an autoantigen in hepatocellular carcinoma patients. This gene has been identified as a potential candidate for X-linked cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ZC4H2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant X-64917866-G-T is Benign according to our data. Variant chrX-64917866-G-T is described in ClinVar as [Benign]. Clinvar id is 707771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00118 (131/111482) while in subpopulation AFR AF= 0.00424 (130/30651). AF 95% confidence interval is 0.00365. There are 0 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 38 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC4H2	NM_018684.4 link	c.592C>A	p.Arg198Arg	synonymous_variant	5/5	ENST00000374839.8	NP_061154.1	Q9NQZ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC4H2	ENST00000374839.8 link	c.592C>A	p.Arg198Arg	synonymous_variant	5/5	1	NM_018684.4	ENSP00000363972.3		Q9NQZ6-1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

131

AN:

111427

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

33613

show subpopulations

Gnomad AFR

AF:

0.00425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000956

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:

0.00

GnomAD3 exomes

AF:

0.000323

AC:

AN:

179616

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

64290

show subpopulations

Gnomad AFR exome

AF:

0.00402

Gnomad AMR exome

AF:

0.000185

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:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

135

AN:

1096711

Hom.:

Cov.:

AF XY:

0.0000773

AC XY:

AN XY:

362123

show subpopulations

Gnomad4 AFR exome

AF:

0.00402

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000143

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.00118

AC:

131

AN:

111482

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

33678

show subpopulations

Gnomad4 AFR

AF:

0.00424

Gnomad4 AMR

AF:

0.0000955

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:

0.00

Alfa

AF:

0.000434

Hom.:

Bravo

AF:

0.00136

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2025	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 09, 2021	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2018

This alteration is classified as 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. -

ZC4H2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 18, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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