13-20160281-C-T

Variant names:

• chr13-20160281-C-T
• rs7984378
• NM_021954.4:c.-18+609G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021954.4(GJA3):​c.-18+609G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,030 control chromosomes in the GnomAD database, including 19,361 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 0.50 (19361 hom., cov: 32)
• Consequence: GJA3 NM_021954.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJA3	NM_021954.4	c.-18+609G>A		intron_variant	Intron 1 of 1	ENST00000241125.4	NP_068773.2
GJA3	XM_011535048.3	c.-18+985G>A		intron_variant	Intron 1 of 1		XP_011533350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJA3	ENST00000241125.4	c.-18+609G>A		intron_variant	Intron 1 of 1	3	NM_021954.4	ENSP00000241125.3

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75272 AN: 151912 Hom.: 19354 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.495 AC: 75322 AN: 152030 Hom.: 19361 Cov.: 32 AF XY: 0.488 AC XY: 36246 AN XY: 74312

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.0823

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.465

Alfa AF: 0.527 Hom.: 10643

Bravo AF: 0.489

Asia WGS AF: 0.255 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.086
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7984378; hg19: chr13-20734420;