rs4769953

Variant names:

• chr13-20141738-C-T
• rs4769953
• NM_021954.4:c.*243G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-20141738-C-T
• chr13-20141738-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021954.4(GJA3):​c.*243G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 576,040 control chromosomes in the GnomAD database, including 18,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3724 hom., cov: 31)
  • Exomes 𝑓: 0.24 (14598 hom.)
• Consequence: GJA3 NM_021954.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.523
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• cataract 14 multiple types

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• early-onset nuclear cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset posterior polar cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pulverulent cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000299362 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 13-20141738-C-T is Benign according to our data. Variant chr13-20141738-C-T is described in ClinVar as Benign. ClinVar VariationId is 311327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021954.4. 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
	GJA3	NM_021954.4	MANE Select	c.*243G>A		3_prime_UTR	Exon 2 of 2	NP_068773.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJA3	ENST00000241125.4	TSL:3 MANE Select	c.*243G>A		3_prime_UTR	Exon 2 of 2	ENSP00000241125.3	Q9Y6H8
	GJA3	ENST00000890229.1		c.*243G>A		3_prime_UTR	Exon 2 of 2	ENSP00000560288.1
	GJA3	ENST00000890230.1		c.*243G>A		3_prime_UTR	Exon 2 of 2	ENSP00000560289.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29718 AN: 151828 Hom.: 3728 Cov.: 31

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.243 AC: 103252 AN: 424094 Hom.: 14598 Cov.: 5 AF XY: 0.246 AC XY: 53999 AN XY: 219788

African (AFR) AF: 0.0678 AC: 699 AN: 10304

American (AMR) AF: 0.393 AC: 5915 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 2977 AN: 12534

East Asian (EAS) AF: 0.501 AC: 13493 AN: 26958

South Asian (SAS) AF: 0.315 AC: 10754 AN: 34130

European-Finnish (FIN) AF: 0.229 AC: 6161 AN: 26862

Middle Eastern (MID) AF: 0.190 AC: 356 AN: 1878

European-Non Finnish (NFE) AF: 0.212 AC: 57502 AN: 271632

Other (OTH) AF: 0.218 AC: 5395 AN: 24732

GnomAD4 genome AF: 0.196 AC: 29708 AN: 151946 Hom.: 3724 Cov.: 31 AF XY: 0.202 AC XY: 15036 AN XY: 74270

African (AFR) AF: 0.0695 AC: 2883 AN: 41504

American (AMR) AF: 0.322 AC: 4922 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3470

East Asian (EAS) AF: 0.427 AC: 2184 AN: 5112

South Asian (SAS) AF: 0.327 AC: 1570 AN: 4798

European-Finnish (FIN) AF: 0.224 AC: 2367 AN: 10566

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.211 AC: 14353 AN: 67918

Other (OTH) AF: 0.177 AC: 374 AN: 2108

Alfa AF: 0.221 Hom.: 2781

Bravo AF: 0.199

Asia WGS AF: 0.352 AC: 1224 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cataract 14 multiple types (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.8
DANN	Benign	0.82
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4769953; hg19: chr13-20715877; COSMIC: COSV53835058;