rs3743123

Positions:

• chr15-34752856-G-A
• chr15-34752856-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020660.3(GJD2):​c.588C>T​(p.Ser196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,613,800 control chromosomes in the GnomAD database, including 81,562 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 0.31 (7331 hom., cov: 31)
  • Exomes 𝑓: 0.32 (74231 hom.)
• Consequence: GJD2 NM_020660.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597

Genes affected

GJD2 (HGNC:19154): (gap junction protein delta 2) This gene encodes a member of the connexin protein family. Connexins are gap junction proteins which are arranged in groups of 6 around a central pore to form a connexon, a component of the gap junction intercellular channel. The channels formed by this protein allow cationic molecule exchange between human beta cells and may function in the regulation of insulin secretion. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=0.597 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJD2	NM_020660.3	c.588C>T	p.Ser196=	synonymous_variant	2/2	ENST00000290374.5	NP_065711.1
GJD2	XM_017022438.2	c.435C>T	p.Ser145=	synonymous_variant	2/2		XP_016877927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJD2	ENST00000290374.5	c.588C>T	p.Ser196=	synonymous_variant	2/2	1	NM_020660.3	ENSP00000290374	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46916 AN: 151910 Hom.: 7332 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.333

GnomAD3 exomes AF: 0.323 AC: 81127 AN: 251476 Hom.: 13503 AF XY: 0.326 AC XY: 44290 AN XY: 135908

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.365

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.246

Gnomad SAS exome AF: 0.423

Gnomad FIN exome AF: 0.280

Gnomad NFE exome AF: 0.304

Gnomad OTH exome AF: 0.331

GnomAD4 exome AF: 0.316 AC: 462304 AN: 1461772 Hom.: 74231 Cov.: 39 AF XY: 0.319 AC XY: 232027 AN XY: 727192

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.330

Gnomad4 SAS exome AF: 0.418

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.309 AC: 46938 AN: 152028 Hom.: 7331 Cov.: 31 AF XY: 0.309 AC XY: 22981 AN XY: 74300

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.335

Alfa AF: 0.312 Hom.: 5967

Bravo AF: 0.309

Asia WGS AF: 0.371 AC: 1288 AN: 3478

EpiCase AF: 0.316

EpiControl AF: 0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.9
DANN	Benign	0.81

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: rs3743123; hg19: chr15-35045057; COSMIC: COSV51747704; COSMIC: COSV51747704;