Variant 7-99929608-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_181538.3(GJC3):c.13T>G(p.Phe5Val) variant causes a missense change. The variant allele was found at a frequency of 0.000312 in 1,607,270 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

GJC3
NM_181538.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.99

Variant links:

Genes affected

GJC3 (HGNC:17495): (gap junction protein gamma 3) This gene encodes a gap junction protein. The encoded protein, also known as a connexin, plays a role in formation of gap junctions, which provide direct connections between neighboring cells. Mutations in this gene have been reported to be associated with nonsyndromic hearing loss.[provided by RefSeq, Feb 2010]

GJC3 links:

ENSG00000237640 (HGNC:):

ENSG00000237640 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02090785).

BP6

Variant 7-99929608-A-C is Benign according to our data. Variant chr7-99929608-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3052339.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJC3	NM_181538.3 linkuse as main transcript	c.13T>G	p.Phe5Val	missense_variant	1/2	ENST00000312891.3	NP_853516.1	Q8NFK1
GJC3	XM_047420329.1 linkuse as main transcript	c.13T>G	p.Phe5Val	missense_variant	1/3		XP_047276285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJC3	ENST00000312891.3 linkuse as main transcript	c.13T>G	p.Phe5Val	missense_variant	1/2	1	NM_181538.3	ENSP00000325775.2		Q8NFK1
ENSG00000237640	ENST00000456499.1 linkuse as main transcript	n.217A>C		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

255

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00588

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.00143

GnomAD3 exomes

AF:

0.000381

AC:

AN:

233654

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

128496

show subpopulations

Gnomad AFR exome

AF:

0.00582

Gnomad AMR exome

AF:

0.000237

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000344

GnomAD4 exome

AF:

0.000169

AC:

246

AN:

1454948

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

723838

show subpopulations

Gnomad4 AFR exome

AF:

0.00628

Gnomad4 AMR exome

AF:

0.000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.00167

AC:

255

AN:

152322

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

109

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00587

Gnomad4 AMR

AF:

0.000523

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:

0.00142

Alfa

AF:

0.000178

Hom.:

Bravo

AF:

0.00203

ESP6500AA

AF:

0.00281

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000387

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GJC3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 13, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.57

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.52

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.021

MetaSVM

Pathogenic

0.83

MutationAssessor

Uncertain

2.7

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.36

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.018

Polyphen

0.10

Vest4

0.67

MVP

0.59

MPC

0.30

ClinPred

0.17

GERP RS

0.88

Varity_R

0.50

gMVP

0.84

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