Variant 19-47066768-G-A 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.3500C>T(p.Thr1167Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00044 in 1,602,948 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 1 hom. )

Consequence

ZC3H4
NM_015168.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.329

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005391538).

BP6

Variant 19-47066768-G-A is Benign according to our data. Variant chr19-47066768-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041020.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 220 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H4	NM_015168.2 linkuse as main transcript	c.3500C>T	p.Thr1167Met	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.3500C>T	p.Thr1167Met	missense_variant	15/15	1	NM_015168.2	P1
ZC3H4	ENST00000601973.1 linkuse as main transcript	c.2321C>T	p.Thr774Met	missense_variant	8/8	5
ZC3H4	ENST00000594019.5 linkuse as main transcript	n.1350C>T		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

220

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00417

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000574

AC:

133

AN:

231786

Hom.:

AF XY:

0.000526

AC XY:

AN XY:

127308

show subpopulations

Gnomad AFR exome

AF:

0.00444

Gnomad AMR exome

AF:

0.000805

Gnomad ASJ exome

AF:

0.00103

Gnomad EAS exome

AF:

0.000114

Gnomad SAS exome

AF:

0.0000679

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.000696

GnomAD4 exome

AF:

0.000334

AC:

485

AN:

1450580

Hom.:

Cov.:

AF XY:

0.000291

AC XY:

210

AN XY:

721662

show subpopulations

Gnomad4 AFR exome

AF:

0.00383

Gnomad4 AMR exome

AF:

0.000860

Gnomad4 ASJ exome

AF:

0.000540

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000468

Gnomad4 FIN exome

AF:

0.0000653

Gnomad4 NFE exome

AF:

0.000215

Gnomad4 OTH exome

AF:

0.000698

GnomAD4 genome

AF:

0.00145

AC:

221

AN:

152368

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00418

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000948

Hom.:

Bravo

AF:

0.00189

ESP6500AA

AF:

0.00271

AC:

ESP6500EA

AF:

0.000240

AC:

ExAC

AF:

0.000596

AC:

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

Apr 11, 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

0.092

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.60

Cadd

Benign

7.4

Dann

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.63

M_CAP

Benign

0.028

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

REVEL

Benign

0.15

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.059

Polyphen

1.0

Vest4

0.10

MVP

0.043

MPC

0.11

ClinPred

0.012

GERP RS

0.19

Varity_R

0.024

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