chr17-40363115-G-A

Variant names:

• chr17-40363115-G-A
• rs1485418857
• NM_152219.4:c.701C>T

Variant summary

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

The NM_152219.4(GJD3):​c.701C>T​(p.Ala234Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000851 in 1,175,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: GJD3 NM_152219.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.651
• 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.701C>T	p.Ala234Val	missense	Exon 1 of 1	NP_689343.3
	GJD3-AS1	NR_186704.1		n.271G>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.701C>T	p.Ala234Val	missense	Exon 1 of 1	ENSP00000463752.1	Q8N144-1
	GJD3-AS1	ENST00000578774.1	TSL:4	n.516G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 30672 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.51e-7 AC: 1 AN: 1175546 Hom.: 0 Cov.: 33 AF XY: 0.00000175 AC XY: 1 AN XY: 570952

African (AFR) AF: 0.00 AC: 0 AN: 24340

American (AMR) AF: 0.00 AC: 0 AN: 13502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17770

East Asian (EAS) AF: 0.0000369 AC: 1 AN: 27072

South Asian (SAS) AF: 0.00 AC: 0 AN: 47528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26790

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 966962

Other (OTH) AF: 0.00 AC: 0 AN: 47272

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.0049	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.39	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	0.058	D
MutationAssessor	Benign	0.81	L
PhyloP100		0.65
Sift4G	Benign	0.22	T
Polyphen		0.48	P
Vest4		0.028
MutPred		0.20		Loss of helix (P = 0.1299)
MVP		0.41
MPC		1.3
ClinPred		0.37	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.029
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.40		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1485418857; hg19: chr17-38519367;