rs74607195

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021954.4(GJA3):c.543C>T(p.Cys181Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,613,678 control chromosomes in the GnomAD database, including 1,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 153 hom., cov: 33)

Exomes 𝑓: 0.035 ( 1316 hom. )

Consequence

GJA3
NM_021954.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0710

Variant links:

Genes affected

GJA3 (HGNC:4277): (gap junction protein alpha 3) The protein encoded by this gene is a connexin and is a component of lens fiber gap junctions. Defects in this gene are a cause of zonular pulverulent cataract type 3 (CZP3). [provided by RefSeq, Jan 2010]

GJA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 13-20142746-G-A is Benign according to our data. Variant chr13-20142746-G-A is described in ClinVar as [Benign]. Clinvar id is 261458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-20142746-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.071 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0324 (4929/152336) while in subpopulation NFE AF= 0.0415 (2821/68020). AF 95% confidence interval is 0.0402. There are 153 homozygotes in gnomad4. There are 2602 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4929 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJA3	NM_021954.4 link	c.543C>T	p.Cys181Cys	synonymous_variant	Exon 2 of 2	ENST00000241125.4	NP_068773.2	Q9Y6H8
GJA3	XM_011535048.3 link	c.543C>T	p.Cys181Cys	synonymous_variant	Exon 2 of 2		XP_011533350.1	Q9Y6H8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJA3	ENST00000241125.4 link	c.543C>T	p.Cys181Cys	synonymous_variant	Exon 2 of 2	3	NM_021954.4	ENSP00000241125.3		Q9Y6H8

Frequencies

GnomAD3 genomes

AF:

0.0324

AC:

4929

AN:

152218

Hom.:

153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00620

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0415

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.0342

AC:

8576

AN:

250712

Hom.:

318

AF XY:

0.0346

AC XY:

4697

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.00457

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.0215

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00954

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.0413

Gnomad OTH exome

AF:

0.0391

GnomAD4 exome

AF:

0.0354

AC:

51742

AN:

1461342

Hom.:

1316

Cov.:

AF XY:

0.0350

AC XY:

25414

AN XY:

727008

show subpopulations

Gnomad4 AFR exome

AF:

0.00469

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.0230

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0104

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.0369

Gnomad4 OTH exome

AF:

0.0287

GnomAD4 genome

AF:

0.0324

AC:

4929

AN:

152336

Hom.:

153

Cov.:

AF XY:

0.0349

AC XY:

2602

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00618

Gnomad4 AMR

AF:

0.0200

Gnomad4 ASJ

AF:

0.0239

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00890

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.0415

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0367

Hom.:

Bravo

AF:

0.0220

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0334

EpiControl

AF:

0.0320

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cataract 14 multiple types

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.7

DANN

Benign

0.68

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