13-20138607-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_021954.4(GJA3):c.*3373del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,098 control chromosomes in the GnomAD database, including 4,417 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4417 hom., cov: 26)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: GJA3 NM_021954.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.05

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 13-20138607-CA-C is Benign according to our data. Variant chr13-20138607-CA-C is described in ClinVar as [Benign]. Clinvar id is 311285.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJA3	NM_021954.4	c.*3373del		3_prime_UTR_variant	2/2	ENST00000241125.4
GJA3	XM_011535048.3	c.*3373del		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJA3	ENST00000241125.4	c.*3373del		3_prime_UTR_variant	2/2	3	NM_021954.4	P1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33667 AN: 151936 Hom.: 4424 Cov.: 26

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.114 AC: 5 AN: 44 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 4 AN XY: 20

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.221 AC: 33652 AN: 152054 Hom.: 4417 Cov.: 26 AF XY: 0.227 AC XY: 16846 AN XY: 74326

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.206

Alfa AF: 0.221 Hom.: 486

Bravo AF: 0.226

Asia WGS AF: 0.366 AC: 1273 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Zonular Pulverulent Cataract Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs144410256; hg19: chr13-20712746;