rs595652

Variant names:

• chr10-35608029-G-A
• rs595652
• NM_153368.3:c.516G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-35608029-G-A
• chr10-35608029-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_153368.3(GJD4):​c.516G>A​(p.Lys172Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,610,496 control chromosomes in the GnomAD database, including 45,477 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 0.19 (3370 hom., cov: 32)
  • Exomes 𝑓: 0.23 (42107 hom.)
• Consequence: GJD4 NM_153368.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 11 publications found

Genes affected

GJD4 (HGNC:23296): (gap junction protein delta 4) Connexins, such as GJD4, are involved in the formation of gap junctions, intercellular conduits that directly connect the cytoplasms of contacting cells. Each gap junction channel is formed by docking of 2 hemichannels, each of which contains 6 connexin subunits (Sohl et al., 2003 [PubMed 12881038]).[supplied by OMIM, Mar 2008]

ENSG00000273312 (HGNC:58343):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-2.79 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJD4	NM_153368.3	c.516G>A	p.Lys172Lys	synonymous_variant	Exon 2 of 2	ENST00000321660.2	NP_699199.2
GJD4-AS1	NR_199599.1	n.165C>T		non_coding_transcript_exon_variant	Exon 1 of 2
GJD4-AS1	NR_199600.1	n.165C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJD4	ENST00000321660.2	c.516G>A	p.Lys172Lys	synonymous_variant	Exon 2 of 2	1	NM_153368.3	ENSP00000315070.1
ENSG00000273312	ENST00000609313.1	n.125C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000273312	ENST00000635993.1	n.-7C>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28488 AN: 152080 Hom.: 3367 Cov.: 32

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.182

GnomAD2 exomes AF: 0.246 AC: 60544 AN: 245754 AF XY: 0.249

Gnomad AFR exome AF: 0.0389

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.345

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.234 AC: 341746 AN: 1458300 Hom.: 42107 Cov.: 36 AF XY: 0.236 AC XY: 171444 AN XY: 725414

African (AFR) AF: 0.0364 AC: 1211 AN: 33256

American (AMR) AF: 0.287 AC: 12737 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4302 AN: 25968

East Asian (EAS) AF: 0.385 AC: 15224 AN: 39578

South Asian (SAS) AF: 0.293 AC: 25216 AN: 86058

European-Finnish (FIN) AF: 0.292 AC: 15198 AN: 52066

Middle Eastern (MID) AF: 0.195 AC: 1123 AN: 5752

European-Non Finnish (NFE) AF: 0.228 AC: 253714 AN: 1110918

Other (OTH) AF: 0.216 AC: 13021 AN: 60250

GnomAD4 genome AF: 0.187 AC: 28500 AN: 152196 Hom.: 3370 Cov.: 32 AF XY: 0.194 AC XY: 14456 AN XY: 74398

African (AFR) AF: 0.0466 AC: 1938 AN: 41562

American (AMR) AF: 0.223 AC: 3412 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1819 AN: 5146

South Asian (SAS) AF: 0.290 AC: 1399 AN: 4822

European-Finnish (FIN) AF: 0.301 AC: 3189 AN: 10604

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15448 AN: 67984

Other (OTH) AF: 0.182 AC: 383 AN: 2108

Alfa AF: 0.177 Hom.: 1643

Bravo AF: 0.177

Asia WGS AF: 0.294 AC: 1022 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	0.19
DANN	Benign	0.82
PhyloP100		-2.8
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: rs595652; hg19: chr10-35896957; COSMIC: COSV58701889; COSMIC: COSV58701889;