17-40363294-C-A

Variant names:

• chr17-40363294-C-A
• rs567452990
• NM_152219.4:c.522G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152219.4(GJD3):​c.522G>T​(p.Pro174Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000798 in 1,253,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P174P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: GJD3 NM_152219.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).

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.522G>T	p.Pro174Pro	synonymous	Exon 1 of 1	NP_689343.3
	GJD3-AS1	NR_186704.1		n.450C>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.522G>T	p.Pro174Pro	synonymous	Exon 1 of 1	ENSP00000463752.1	Q8N144-1
	GJD3-AS1	ENST00000578774.1	TSL:4	n.695C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.98e-7 AC: 1 AN: 1253662 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 615290

African (AFR) AF: 0.00 AC: 0 AN: 25546

American (AMR) AF: 0.00 AC: 0 AN: 20682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20960

East Asian (EAS) AF: 0.00 AC: 0 AN: 27470

South Asian (SAS) AF: 0.00 AC: 0 AN: 65264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5172

European-Non Finnish (NFE) AF: 9.94e-7 AC: 1 AN: 1006264

Other (OTH) AF: 0.00 AC: 0 AN: 51058

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	15
DANN	Benign	0.94
PhyloP100		-0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs567452990; hg19: chr17-38519546;