Variant chr6-87284470-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_198568.3(GJB7):c.443G>C(p.Gly148Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00044 in 1,613,850 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00061 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

GJB7
NM_198568.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.76

Variant links:

Genes affected

GJB7 (HGNC:16690): (gap junction protein beta 7) Connexins, such as GJB7, 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]

GJB7 links:

LOC124901356 (HGNC:):

LOC124901356 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4079122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJB7	NM_198568.3 linkuse as main transcript	c.443G>C	p.Gly148Ala	missense_variant	3/3	ENST00000525899.6	NP_940970.1	Q6PEY0
LOC124901356	XR_007059667.1 linkuse as main transcript	n.692-156C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJB7	ENST00000525899.6 linkuse as main transcript	c.443G>C	p.Gly148Ala	missense_variant	3/3	1	NM_198568.3	ENSP00000435355.1		Q6PEY0
GJB7	ENST00000369576.2 linkuse as main transcript	c.443G>C	p.Gly148Ala	missense_variant	2/2	4		ENSP00000358589.2		A0A0A0MRM5

Frequencies

GnomAD3 genomes

AF:

0.000612

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

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:

0.000838

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000291

AC:

AN:

251132

Hom.:

AF XY:

0.000273

AC XY:

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000467

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000422

AC:

617

AN:

1461812

Hom.:

Cov.:

AF XY:

0.000399

AC XY:

290

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000519

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000612

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.000687

AC XY:

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.0000967

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000573

Hom.:

Bravo

AF:

0.000533

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.443G>C (p.G148A) alteration is located in exon 3 (coding exon 1) of the GJB7 gene. This alteration results from a G to C substitution at nucleotide position 443, causing the glycine (G) at amino acid position 148 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Uncertain

0.11

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Uncertain

0.68

D;.

Eigen

Benign

-0.083

Eigen_PC

Benign

-0.070

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.075

MetaRNN

Benign

0.41

T;T

MetaSVM

Uncertain

0.75

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.2

D;D

REVEL

Pathogenic

0.67

Sift

Uncertain

0.014

D;D

Sift4G

Uncertain

0.011

D;.

Polyphen

0.12

B;.

Vest4

0.56

MVP

0.79

MPC

0.023

ClinPred

0.095

GERP RS

4.1

Varity_R

0.63

gMVP

0.64

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