Variant 19-47066949-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015168.2(ZC3H4):c.3319G>A(p.Ala1107Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,593,208 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

ZC3H4
NM_015168.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.647

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013034493).

BP6

Variant 19-47066949-C-T is Benign according to our data. Variant chr19-47066949-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3039780.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H4	NM_015168.2 linkuse as main transcript	c.3319G>A	p.Ala1107Thr	missense_variant	15/15	ENST00000253048.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZC3H4	ENST00000253048.10 linkuse as main transcript	c.3319G>A	p.Ala1107Thr	missense_variant	15/15	1	NM_015168.2	P1
ZC3H4	ENST00000601973.1 linkuse as main transcript	c.2140G>A	p.Ala714Thr	missense_variant	8/8	5
ZC3H4	ENST00000594019.5 linkuse as main transcript	n.1169G>A		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.000697

AC:

106

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00106

AC:

230

AN:

216688

Hom.:

AF XY:

0.00113

AC XY:

135

AN XY:

119746

show subpopulations

Gnomad AFR exome

AF:

0.000161

Gnomad AMR exome

AF:

0.000218

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00133

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.00183

Gnomad OTH exome

AF:

0.000934

GnomAD4 exome

AF:

0.00115

AC:

1656

AN:

1440974

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

857

AN XY:

715124

show subpopulations

Gnomad4 AFR exome

AF:

0.000211

Gnomad4 AMR exome

AF:

0.000232

Gnomad4 ASJ exome

AF:

0.0000393

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.000192

Gnomad4 NFE exome

AF:

0.00130

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.000696

AC:

106

AN:

152234

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000846

Hom.:

Bravo

AF:

0.000608

ExAC

AF:

0.00136

AC:

162

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ZC3H4-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 12, 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

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.80

Cadd

Benign

7.5

Dann

Benign

0.93

DEOGEN2

Benign

0.11

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.58

M_CAP

Benign

0.011

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.2

REVEL

Benign

0.076

Sift

Benign

0.14

Sift4G

Benign

0.45

Polyphen

0.97

Vest4

0.027

MVP

0.11

MPC

0.11

ClinPred

0.0098

GERP RS

-4.7

Varity_R

0.037

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