17-40363377-C-A

Variant names:

• chr17-40363377-C-A
• rs915850550
• NM_152219.4:c.439G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152219.4(GJD3):​c.439G>T​(p.Glu147*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000401 in 1,247,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: GJD3 NM_152219.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.16
• Publications: 1 publications found

Genes affected

GJD3 (HGNC:19147): (gap junction protein delta 3) This gene is a member of the large family of connexins that are required for the formation of gap junctions. Six connexin monomers form a hemichannel, or connexon, on the cell surface. This connexon can interact with a connexon from a neighboring cell, thus forming a channel linking the cytoplasm of the 2 cells. [provided by RefSeq, Jul 2008]

GJD3-AS1 (HGNC:56092): (GJD3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152219.4. 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
	GJD3	NM_152219.4	MANE Select	c.439G>T	p.Glu147*	stop_gained	Exon 1 of 1	NP_689343.3
	GJD3-AS1	NR_186704.1		n.533C>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJD3	ENST00000578689.2	TSL:6 MANE Select	c.439G>T	p.Glu147*	stop_gained	Exon 1 of 1	ENSP00000463752.1	Q8N144-1
	GJD3-AS1	ENST00000578774.1	TSL:4	n.778C>A		non_coding_transcript_exon	Exon 2 of 2
	GJD3-AS1	ENST00000791155.1		n.-193C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000194 AC: 1 AN: 51536 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000511

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000401 AC: 5 AN: 1247800 Hom.: 0 Cov.: 33 AF XY: 0.00000326 AC XY: 2 AN XY: 613398

African (AFR) AF: 0.00 AC: 0 AN: 25242

American (AMR) AF: 0.00 AC: 0 AN: 18070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20586

East Asian (EAS) AF: 0.00 AC: 0 AN: 27508

South Asian (SAS) AF: 0.00 AC: 0 AN: 61274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4634

European-Non Finnish (NFE) AF: 0.00000496 AC: 5 AN: 1007962

Other (OTH) AF: 0.00 AC: 0 AN: 50768

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Pathogenic	0.80
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		7.2
Vest4		0.18
GERP RS		3.0
Mutation Taster		=45/155	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs915850550; hg19: chr17-38519629;