chr13-20145283-T-G

Variant names:

• chr13-20145283-T-G
• rs7329467
• NM_021954.4:c.-17-1978A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021954.4(GJA3):​c.-17-1978A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,052 control chromosomes in the GnomAD database, including 2,920 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2920 hom., cov: 32)
• Consequence: GJA3 NM_021954.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 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.-17-1978A>C		intron	N/A	NP_068773.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJA3	ENST00000241125.4	TSL:3 MANE Select	c.-17-1978A>C		intron	N/A	ENSP00000241125.3	Q9Y6H8
	GJA3	ENST00000890229.1		c.-17-1978A>C		intron	N/A	ENSP00000560288.1
	GJA3	ENST00000890230.1		c.-17-1978A>C		intron	N/A	ENSP00000560289.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25737 AN: 151934 Hom.: 2911 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0978

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25772 AN: 152052 Hom.: 2920 Cov.: 32 AF XY: 0.168 AC XY: 12509 AN XY: 74342

African (AFR) AF: 0.316 AC: 13091 AN: 41428

American (AMR) AF: 0.0915 AC: 1399 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0978 AC: 472 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2050 AN: 10566

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8034 AN: 67984

Other (OTH) AF: 0.135 AC: 284 AN: 2104

Alfa AF: 0.119 Hom.: 2167

Bravo AF: 0.166

Asia WGS AF: 0.0620 AC: 215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.65
PhyloP100		0.13
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: rs7329467; hg19: chr13-20719422;