Variant X-137566710-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003413.4(ZIC3):c.19G>A(p.Gly7Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000334 in 1,198,483 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 0.0000028 ( 0 hom. 0 hem. )

Consequence

ZIC3
NM_003413.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.29

Variant links:

Genes affected

ZIC3 (HGNC:12874): (Zic family member 3) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation. Mutations in this gene cause X-linked visceral heterotaxy, which includes congenital heart disease and left-right axis defects in organs. [provided by RefSeq, Jul 2008]

ZIC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.119133145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC3	NM_003413.4 link	c.19G>A	p.Gly7Arg	missense_variant	Exon 1 of 3	ENST00000287538.10	NP_003404.1
ZIC3	NM_001330661.1 link	c.19G>A	p.Gly7Arg	missense_variant	Exon 1 of 3		NP_001317590.1	O60481-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC3	ENST00000287538.10 link	c.19G>A	p.Gly7Arg	missense_variant	Exon 1 of 3	1	NM_003413.4	ENSP00000287538.5		O60481-1
ZIC3	ENST00000370606.3 link	c.19G>A	p.Gly7Arg	missense_variant	Exon 1 of 3	5		ENSP00000359638.3		O60481-2

Frequencies

GnomAD3 genomes

AF:

0.00000885

AC:

AN:

112969

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35111

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000652

AC:

AN:

153469

Hom.:

AF XY:

0.00

AC XY:

AN XY:

47917

show subpopulations

Gnomad AFR exome

AF:

0.0000911

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1085514

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

354396

show subpopulations

Gnomad4 AFR exome

AF:

0.0000763

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000885

AC:

AN:

112969

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35111

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000832

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.58

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

1.0

D;.

Vest4

0.21

MutPred

0.14

Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);

MVP

0.16

MPC

2.2

ClinPred

0.39

GERP RS

3.2

Varity_R

0.40

gMVP

0.54

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over