rs1220445871

Variant names:

• chr17-40362980-C-A
• rs1220445871
• NM_152219.4:c.836G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-40362980-C-A
• chr17-40362980-C-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.836G>T​(p.Gly279Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000922 in 1,084,110 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: 33)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: GJD3 NM_152219.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.965
• Publications: 0 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 (MetaRNN=0.0980922).

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.836G>T	p.Gly279Val	missense	Exon 1 of 1	NP_689343.3
	GJD3-AS1	NR_186704.1		n.136C>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.836G>T	p.Gly279Val	missense	Exon 1 of 1	ENSP00000463752.1	Q8N144-1
	GJD3-AS1	ENST00000578774.1	TSL:4	n.484-103C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.22e-7 AC: 1 AN: 1084110 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 519752

African (AFR) AF: 0.00 AC: 0 AN: 21876

American (AMR) AF: 0.00 AC: 0 AN: 9124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13714

East Asian (EAS) AF: 0.00 AC: 0 AN: 23726

South Asian (SAS) AF: 0.00 AC: 0 AN: 28944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2954

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 919964

Other (OTH) AF: 0.00 AC: 0 AN: 42306

GnomAD4 genome Cov.: 33

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	0.13
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.098	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.96
PrimateAI	Uncertain	0.78	T
Sift4G	Benign	0.13	T
Polyphen		0.047	B
Vest4		0.13
MVP		0.84
MPC		1.9
GERP RS		0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.055
gMVP		0.16
Mutation Taster		=90/10	polymorphism

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: rs1220445871; hg19: chr17-38519232;