rs1886176

Variant names:

• chr13-20141662-C-A
• rs1886176
• NM_021954.4:c.*319G>T

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.*319G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 380,100 control chromosomes in the GnomAD database, including 12,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4789 hom., cov: 30)
  • Exomes 𝑓: 0.24 (7378 hom.)
• Consequence: GJA3 NM_021954.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.628
• Publications: 14 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=-0.8).
• BP6: Variant 13-20141662-C-A is Benign according to our data. Variant chr13-20141662-C-A is described in ClinVar as Benign. ClinVar VariationId is 311326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 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.*319G>T		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.*319G>T		3_prime_UTR	Exon 2 of 2	ENSP00000241125.3	Q9Y6H8
	GJA3	ENST00000890229.1		c.*319G>T		3_prime_UTR	Exon 2 of 2	ENSP00000560288.1
	GJA3	ENST00000890230.1		c.*319G>T		3_prime_UTR	Exon 2 of 2	ENSP00000560289.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37608 AN: 151704 Hom.: 4783 Cov.: 30

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.243 AC: 55563 AN: 228278 Hom.: 7378 Cov.: 2 AF XY: 0.244 AC XY: 28462 AN XY: 116710

African (AFR) AF: 0.197 AC: 1213 AN: 6146

American (AMR) AF: 0.185 AC: 1625 AN: 8804

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 1690 AN: 7860

East Asian (EAS) AF: 0.280 AC: 4518 AN: 16144

South Asian (SAS) AF: 0.218 AC: 3419 AN: 15712

European-Finnish (FIN) AF: 0.221 AC: 2949 AN: 13318

Middle Eastern (MID) AF: 0.300 AC: 337 AN: 1124

European-Non Finnish (NFE) AF: 0.250 AC: 36069 AN: 144468

Other (OTH) AF: 0.255 AC: 3743 AN: 14702

GnomAD4 genome AF: 0.248 AC: 37631 AN: 151822 Hom.: 4789 Cov.: 30 AF XY: 0.248 AC XY: 18366 AN XY: 74158

African (AFR) AF: 0.204 AC: 8445 AN: 41392

American (AMR) AF: 0.229 AC: 3490 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 770 AN: 3466

East Asian (EAS) AF: 0.350 AC: 1798 AN: 5138

South Asian (SAS) AF: 0.264 AC: 1266 AN: 4800

European-Finnish (FIN) AF: 0.243 AC: 2565 AN: 10540

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18326 AN: 67900

Other (OTH) AF: 0.282 AC: 595 AN: 2108

Alfa AF: 0.260 Hom.: 20517

Bravo AF: 0.245

Asia WGS AF: 0.291 AC: 1012 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	-0.80
CADD	Benign	7.4
DANN	Benign	0.78
PhyloP100		0.63
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: rs1886176; hg19: chr13-20715801;