chr13-20139379-A-G

Position:

• chr13-20139379-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021954.4(GJA3):​c.*2602T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,934 control chromosomes in the GnomAD database, including 4,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4755 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: GJA3 NM_021954.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.843

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 13-20139379-A-G is Benign according to our data. Variant chr13-20139379-A-G is described in ClinVar as [Benign]. Clinvar id is 311295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJA3	NM_021954.4	c.*2602T>C		3_prime_UTR_variant	2/2	ENST00000241125.4	NP_068773.2
GJA3	XM_011535048.3	c.*2602T>C		3_prime_UTR_variant	2/2		XP_011533350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJA3	ENST00000241125	c.*2602T>C		3_prime_UTR_variant	2/2	3	NM_021954.4	ENSP00000241125.3

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37380 AN: 151816 Hom.: 4749 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.281

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.246 AC: 37401 AN: 151934 Hom.: 4755 Cov.: 31 AF XY: 0.246 AC XY: 18273 AN XY: 74252

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.284

Alfa AF: 0.255 Hom.: 1985

Bravo AF: 0.243

Asia WGS AF: 0.295 AC: 1023 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Cataract 14 multiple types Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.78

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: rs6490519; hg19: chr13-20713518;