Variant X-64920062-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018684.4(ZC4H2):c.398+19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00704 in 1,202,881 control chromosomes in the GnomAD database, including 33 homozygotes. There are 2,712 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 4 hom., 216 hem., cov: 22)

Exomes 𝑓: 0.0071 ( 29 hom. 2496 hem. )

Consequence

ZC4H2
NM_018684.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.338

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:

ZC4H2 (HGNC:):

ZC4H2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-64920062-C-A is Benign according to our data. Variant chrX-64920062-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 445593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00676 (751/111031) while in subpopulation NFE AF= 0.00824 (437/53011). AF 95% confidence interval is 0.00761. There are 4 homozygotes in gnomad4. There are 216 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC4H2	NM_018684.4 linkuse as main transcript	c.398+19G>T		intron_variant		ENST00000374839.8	NP_061154.1	Q9NQZ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC4H2	ENST00000374839.8 linkuse as main transcript	c.398+19G>T		intron_variant		1	NM_018684.4	ENSP00000363972.3		Q9NQZ6-1

Frequencies

GnomAD3 genomes

AF:

0.00681

AC:

756

AN:

110980

Hom.:

Cov.:

AF XY:

0.00651

AC XY:

216

AN XY:

33196

show subpopulations

Gnomad AFR

AF:

0.000591

Gnomad AMI

AF:

0.00586

Gnomad AMR

AF:

0.00489

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00115

Gnomad FIN

AF:

0.0305

Gnomad MID

AF:

0.0377

Gnomad NFE

AF:

0.00824

Gnomad OTH

AF:

0.00675

GnomAD3 exomes

AF:

0.00778

AC:

1348

AN:

173246

Hom.:

AF XY:

0.00724

AC XY:

426

AN XY:

58808

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00239

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000908

Gnomad FIN exome

AF:

0.0310

Gnomad NFE exome

AF:

0.00799

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.00707

AC:

7722

AN:

1091850

Hom.:

Cov.:

AF XY:

0.00696

AC XY:

2496

AN XY:

358450

show subpopulations

Gnomad4 AFR exome

AF:

0.000951

Gnomad4 AMR exome

AF:

0.00307

Gnomad4 ASJ exome

AF:

0.0153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00125

Gnomad4 FIN exome

AF:

0.0319

Gnomad4 NFE exome

AF:

0.00666

Gnomad4 OTH exome

AF:

0.00690

GnomAD4 genome

AF:

0.00676

AC:

751

AN:

111031

Hom.:

Cov.:

AF XY:

0.00649

AC XY:

216

AN XY:

33257

show subpopulations

Gnomad4 AFR

AF:

0.000589

Gnomad4 AMR

AF:

0.00488

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00116

Gnomad4 FIN

AF:

0.0305

Gnomad4 NFE

AF:

0.00824

Gnomad4 OTH

AF:

0.00666

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00504

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 03, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.0

DANN

Benign

0.36

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