Variant 19-47066656-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_015168.2(ZC3H4):c.3612C>T(p.Ala1204=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000788 in 1,611,784 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00076 ( 12 hom. )

Consequence

ZC3H4
NM_015168.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.88

Variant links:

Genes affected

ZC3H4 (HGNC:17808): (zinc finger CCCH-type containing 4) This gene encodes a member of a family of CCCH (C-x8-C-x5-C-x3-H type) zinc finger domain-containing proteins. These zinc finger domains, which coordinate zinc finger binding and are characterized by three cysteine residues and one histidine residue, are nucleic acid-binding. Other family members are known to function in post-transcriptional regulation. [provided by RefSeq, Aug 2011]

ZC3H4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 19-47066656-G-A is Benign according to our data. Variant chr19-47066656-G-A is described in ClinVar as [Benign]. Clinvar id is 3034160.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.88 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000757 (1105/1459428) while in subpopulation AMR AF= 0.022 (980/44590). AF 95% confidence interval is 0.0208. There are 12 homozygotes in gnomad4_exome. There are 465 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 165 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H4	NM_015168.2 linkuse as main transcript	c.3612C>T	p.Ala1204=	synonymous_variant	15/15	ENST00000253048.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZC3H4	ENST00000253048.10 linkuse as main transcript	c.3612C>T	p.Ala1204=	synonymous_variant	15/15	1	NM_015168.2	P1
ZC3H4	ENST00000601973.1 linkuse as main transcript	c.2433C>T	p.Ala811=	synonymous_variant	8/8	5
ZC3H4	ENST00000594019.5 linkuse as main transcript	n.1462C>T		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

162

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00877

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00366

AC:

875

AN:

239078

Hom.:

AF XY:

0.00277

AC XY:

363

AN XY:

131154

show subpopulations

Gnomad AFR exome

AF:

0.000355

Gnomad AMR exome

AF:

0.0245

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.000395

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.00187

GnomAD4 exome

AF:

0.000757

AC:

1105

AN:

1459428

Hom.:

Cov.:

AF XY:

0.000641

AC XY:

465

AN XY:

725944

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0220

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00103

Gnomad4 SAS exome

AF:

0.0000931

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.000481

GnomAD4 genome

AF:

0.00108

AC:

165

AN:

152356

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00895

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000227

Hom.:

Bravo

AF:

0.00194

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ZC3H4-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 24, 2019

This variant is classified as 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

-0.85

CADD

Benign

0.38

DANN

Benign

0.44

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