Genetic Variant NM_003413.4:c.76G>C (chrX-137566767-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003413.4(ZIC3):c.76G>C(p.Glu26Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,075,140 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000037 ( 0 hom. 1 hem. )

Consequence

ZIC3
NM_003413.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.26

Publications

0 publications found

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:

LINC02931 (HGNC:55853): (long intergenic non-protein coding RNA 2931)

LINC02931 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16931504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003413.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIC3	NM_003413.4	MANE Select	c.76G>C	p.Glu26Gln	missense	Exon 1 of 3	NP_003404.1	O60481-1
	ZIC3	NM_001330661.1		c.76G>C	p.Glu26Gln	missense	Exon 1 of 3	NP_001317590.1	O60481-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZIC3	ENST00000287538.10	TSL:1 MANE Select	c.76G>C	p.Glu26Gln	missense	Exon 1 of 3	ENSP00000287538.5	O60481-1
ZIC3	ENST00000919832.1		c.76G>C	p.Glu26Gln	missense	Exon 4 of 6	ENSP00000589891.1
ZIC3	ENST00000919833.1		c.76G>C	p.Glu26Gln	missense	Exon 4 of 6	ENSP00000589892.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000733

AC:

AN:

136426

AF XY:

0.0000240

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000372

AC:

AN:

1075140

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

349622

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26096

American (AMR)

AF:

0.00

AC:

AN:

32407

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18956

East Asian (EAS)

AF:

0.00

AC:

AN:

29288

South Asian (SAS)

AF:

0.0000194

AC:

AN:

51482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35321

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3977

European-Non Finnish (NFE)

AF:

0.00000240

AC:

AN:

832363

Other (OTH)

AF:

0.0000221

AC:

AN:

45250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

VACTERL association, X-linked, with or without hydrocephalus (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.22

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

6.3

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.70

REVEL

Benign

0.19

Sift

Uncertain

0.0050

Sift4G

Benign

0.22

Polyphen

1.0

Vest4

0.18

MutPred

0.11

Loss of sheet (P = 0.0483)

MVP

0.22

MPC

1.6

ClinPred

0.37

GERP RS

2.3

PromoterAI

0.014

Neutral

(source)

Varity_R

0.20

gMVP

0.41

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over