Variant 10-35607643-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_153368.3(GJD4):c.130G>A(p.Val44Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0081 in 1,614,190 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 65 hom. )

Consequence

GJD4
NM_153368.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

GJD4 (HGNC:23296): (gap junction protein delta 4) Connexins, such as GJD4, are involved in the formation of gap junctions, intercellular conduits that directly connect the cytoplasms of contacting cells. Each gap junction channel is formed by docking of 2 hemichannels, each of which contains 6 connexin subunits (Sohl et al., 2003 [PubMed 12881038]).[supplied by OMIM, Mar 2008]

GJD4 links:

ENSG00000273312 (HGNC:):

ENSG00000273312 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012991011).

BP6

Variant 10-35607643-G-A is Benign according to our data. Variant chr10-35607643-G-A is described in ClinVar as [Benign]. Clinvar id is 2640407.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJD4	NM_153368.3 linkuse as main transcript	c.130G>A	p.Val44Ile	missense_variant	2/2	ENST00000321660.2	NP_699199.2	Q96KN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GJD4	ENST00000321660.2 linkuse as main transcript	c.130G>A	p.Val44Ile	missense_variant	2/2	1	NM_153368.3	ENSP00000315070.1	Q96KN9
ENSG00000273312	ENST00000609313.1 linkuse as main transcript	n.511C>T		non_coding_transcript_exon_variant	1/1	6
ENSG00000273312	ENST00000635993.1 linkuse as main transcript	n.287+93C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00662

AC:

1007

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00824

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00948

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00648

AC:

1628

AN:

251138

Hom.:

AF XY:

0.00626

AC XY:

850

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.0125

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.00783

GnomAD4 exome

AF:

0.00826

AC:

12071

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00812

AC XY:

5908

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00329

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000707

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.00967

Gnomad4 OTH exome

AF:

0.00649

GnomAD4 genome

AF:

0.00661

AC:

1007

AN:

152330

Hom.:

Cov.:

AF XY:

0.00695

AC XY:

518

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00823

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.00948

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00861

Hom.:

Bravo

AF:

0.00564

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00907

AC:

ExAC

AF:

0.00682

AC:

828

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.00788

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

GJD4: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Benign

7.9

DANN

Benign

0.97

DEOGEN2

Uncertain

0.46

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.65

MetaRNN

Benign

0.013

MetaSVM

Uncertain

0.28

MutationAssessor

Benign

0.33

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.24

REVEL

Uncertain

0.32

Sift

Benign

1.0

Sift4G

Benign

0.82

Polyphen

0.73

Vest4

0.083

MVP

0.41

MPC

0.27

ClinPred

0.021

GERP RS

1.5

Varity_R

0.042

gMVP

0.32

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over