Variant 1-38874747-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_030772.5(GJA9):c.1352C>T(p.Thr451Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00474 in 1,614,148 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 140 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 122 hom. )

Consequence

GJA9
NM_030772.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.116

Variant links:

Genes affected

GJA9 (HGNC:19155): (gap junction protein alpha 9) Connexins, such as GJA9, 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]

GJA9 links:

ENSG00000274944 (HGNC:):

ENSG00000274944 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=0.0018621087).

BP6

Variant 1-38874747-G-A is Benign according to our data. Variant chr1-38874747-G-A is described in ClinVar as [Benign]. Clinvar id is 783284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJA9	NM_030772.5 linkuse as main transcript	c.1352C>T	p.Thr451Ile	missense_variant	2/2	ENST00000357771.5	NP_110399.2	P57773-1A0A654IBV8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJA9	ENST00000357771.5 linkuse as main transcript	c.1352C>T	p.Thr451Ile	missense_variant	2/2	1	NM_030772.5	ENSP00000350415.3		P57773-1
ENSG00000274944	ENST00000621281.1 linkuse as main transcript	c.37-1657C>T		intron_variant		2		ENSP00000479064.1		A0A087WV05

Frequencies

GnomAD3 genomes

AF:

0.0232

AC:

3534

AN:

152138

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0786

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00643

AC:

1618

AN:

251472

Hom.:

AF XY:

0.00486

AC XY:

661

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0771

Gnomad AMR exome

AF:

0.00578

Gnomad ASJ exome

AF:

0.00764

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000422

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00282

AC:

4116

AN:

1461892

Hom.:

122

Cov.:

AF XY:

0.00248

AC XY:

1805

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0835

Gnomad4 AMR exome

AF:

0.00633

Gnomad4 ASJ exome

AF:

0.00876

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000510

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000332

Gnomad4 OTH exome

AF:

0.00604

GnomAD4 genome

AF:

0.0233

AC:

3542

AN:

152256

Hom.:

140

Cov.:

AF XY:

0.0232

AC XY:

1726

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0786

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00465

Hom.:

Bravo

AF:

0.0270

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0722

AC:

318

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00749

AC:

909

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000533

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.28

CADD

Benign

6.6

DANN

Benign

0.75

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.40

.;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.099

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.0

B;B

Vest4

0.069

MVP

0.10

MPC

0.11

ClinPred

0.0014

GERP RS

2.3

Varity_R

0.054

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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