Variant 7-99929131-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181538.3(GJC3):c.490C>T(p.Pro164Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,613,838 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 62 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 66 hom. )

Consequence

GJC3
NM_181538.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.43

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004207462).

BP6

Variant 7-99929131-G-A is Benign according to our data. Variant chr7-99929131-G-A is described in ClinVar as [Benign]. Clinvar id is 778326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJC3	NM_181538.3 linkuse as main transcript	c.490C>T	p.Pro164Ser	missense_variant	1/2	ENST00000312891.3	NP_853516.1	Q8NFK1
GJC3	XM_047420329.1 linkuse as main transcript	c.241-217C>T		intron_variant			XP_047276285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJC3	ENST00000312891.3 linkuse as main transcript	c.490C>T	p.Pro164Ser	missense_variant	1/2	1	NM_181538.3	ENSP00000325775.2		Q8NFK1

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2366

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0546

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00400

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00393

AC:

987

AN:

250876

Hom.:

AF XY:

0.00299

AC XY:

406

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.0554

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00156

AC:

2279

AN:

1461600

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

977

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.0581

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.0155

AC:

2367

AN:

152238

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1119

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0545

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.00265

Hom.:

Bravo

AF:

0.0175

ESP6500AA

AF:

0.0558

AC:

246

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00482

AC:

585

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Uncertain

0.66

Eigen

Benign

-0.042

Eigen_PC

Benign

0.0063

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.31

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.9

REVEL

Benign

0.24

Sift

Benign

0.81

Sift4G

Benign

0.17

Polyphen

0.80

Vest4

0.11

MVP

0.79

MPC

0.67

ClinPred

0.013

GERP RS

4.8

Varity_R

0.19

gMVP

0.44

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