Variant 7-99923585-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_181538.3(GJC3):c.800C>T(p.Ala267Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 780,954 control chromosomes in the GnomAD database, including 311 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 (no stars).

Frequency

Genomes: 𝑓 0.022 ( 48 hom., cov: 32)

Exomes 𝑓: 0.025 ( 263 hom. )

Consequence

GJC3
NM_181538.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.365

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:

LOC101927610 (HGNC:):

LOC101927610 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027722716).

BP6

Variant 7-99923585-G-A is Benign according to our data. Variant chr7-99923585-G-A is described in ClinVar as [Benign]. Clinvar id is 3055375.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0218 (3317/152210) while in subpopulation NFE AF= 0.0335 (2280/68004). AF 95% confidence interval is 0.0324. There are 48 homozygotes in gnomad4. There are 1582 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJC3	NM_181538.3 linkuse as main transcript	c.800C>T	p.Ala267Val	missense_variant	2/2	ENST00000312891.3	NP_853516.1	Q8NFK1
GJC3	XM_047420329.1 linkuse as main transcript	c.*1C>T		3_prime_UTR_variant	3/3		XP_047276285.1
LOC101927610	XR_001745295.3 linkuse as main transcript	n.2739G>A		non_coding_transcript_exon_variant	2/2
LOC101927610	XR_001745296.3 linkuse as main transcript	n.2627G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJC3	ENST00000312891.3 linkuse as main transcript	c.800C>T	p.Ala267Val	missense_variant	2/2	1	NM_181538.3	ENSP00000325775.2		Q8NFK1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3318

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00488

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0219

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00871

Gnomad FIN

AF:

0.0278

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0335

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0212

AC:

5279

AN:

249028

Hom.:

AF XY:

0.0217

AC XY:

2927

AN XY:

134808

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.0157

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00954

Gnomad FIN exome

AF:

0.0301

Gnomad NFE exome

AF:

0.0314

Gnomad OTH exome

AF:

0.0225

GnomAD4 exome

AF:

0.0249

AC:

15627

AN:

628744

Hom.:

263

Cov.:

AF XY:

0.0245

AC XY:

8376

AN XY:

342508

show subpopulations

Gnomad4 AFR exome

AF:

0.00430

Gnomad4 AMR exome

AF:

0.0134

Gnomad4 ASJ exome

AF:

0.0153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00979

Gnomad4 FIN exome

AF:

0.0326

Gnomad4 NFE exome

AF:

0.0327

Gnomad4 OTH exome

AF:

0.0234

GnomAD4 genome

AF:

0.0218

AC:

3317

AN:

152210

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

1582

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00486

Gnomad4 AMR

AF:

0.0218

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00851

Gnomad4 FIN

AF:

0.0278

Gnomad4 NFE

AF:

0.0335

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0278

Hom.:

Bravo

AF:

0.0195

TwinsUK

AF:

0.0289

AC:

107

ALSPAC

AF:

0.0291

AC:

112

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0308

AC:

265

ExAC

AF:

0.0215

AC:

2617

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0290

EpiControl

AF:

0.0285

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GJC3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2019

This variant is classified as 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

0.080

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.32

CADD

Benign

7.7

DANN

Benign

0.63

DEOGEN2

Benign

0.048

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0028

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.79

REVEL

Benign

0.25

Sift

Benign

0.14

Sift4G

Benign

0.13

Polyphen

0.59

Vest4

0.028

MPC

0.23

ClinPred

0.013

GERP RS

0.23

Varity_R

0.078

gMVP

0.041

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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