dbSNP rs928521554: GJD3:p.Glu275Gln (chr17-40362993-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152219.4(GJD3):c.823G>C(p.Glu275Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000492 in 1,220,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E275K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

GJD3
NM_152219.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.441

Variant links:

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 links:

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

GJD3-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12358013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJD3	NM_152219.4 link	c.823G>C	p.Glu275Gln	missense_variant	Exon 1 of 1	ENST00000578689.2	NP_689343.3	Q8N144-1A0A654IC68
GJD3-AS1	NR_186704.1 link	n.149C>G		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJD3	ENST00000578689.2 link	c.823G>C	p.Glu275Gln	missense_variant	Exon 1 of 1	6	NM_152219.4	ENSP00000463752.1		Q8N144-1
GJD3-AS1	ENST00000578774.1 link	n.484-90C>G		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151360

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000187

AC:

AN:

1068784

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

509898

show subpopulations

Gnomad4 AFR exome

AF:

0.0000462

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000110

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151360

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73918

show subpopulations

Gnomad4 AFR

AF:

0.0000968

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

0.0035

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.092

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.47

M_CAP

Benign

0.027

MetaRNN

Benign

0.12

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.82

Sift4G

Benign

0.36

Polyphen

0.45

Vest4

0.067

MVP

0.87

MPC

1.5

GERP RS

2.2

Varity_R

0.077

gMVP

0.30

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over