Variant 1-38874709-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000357771.5(GJA9):c.1390T>C(p.Ser464Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00705 in 1,614,154 control chromosomes in the GnomAD database, including 57 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 0.0052 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 55 hom. )

Consequence

GJA9
ENST00000357771.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.369

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:

RRAGC-DT (HGNC:55793): (RRAGC divergent transcript)

RRAGC-DT links:

GJA9-MYCBP (HGNC:):

GJA9-MYCBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026267767).

BP6

Variant 1-38874709-A-G is Benign according to our data. Variant chr1-38874709-A-G is described in ClinVar as [Benign]. Clinvar id is 772681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GJA9	NM_030772.5 linkuse as main transcript	c.1390T>C	p.Ser464Pro	missense_variant	2/2	ENST00000357771.5	NP_110399.2
GJA9-MYCBP	NR_037637.1 linkuse as main transcript	n.195+6723T>C		intron_variant, non_coding_transcript_variant
LOC105378663	NR_135048.1 linkuse as main transcript	n.179+1130A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJA9	ENST00000357771.5 linkuse as main transcript	c.1390T>C	p.Ser464Pro	missense_variant	2/2	1	NM_030772.5	ENSP00000350415	P1	P57773-1
RRAGC-DT	ENST00000667635.1 linkuse as main transcript	n.267+14470A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00521

AC:

792

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.0156

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00656

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00676

AC:

1700

AN:

251488

Hom.:

AF XY:

0.00708

AC XY:

962

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00361

Gnomad ASJ exome

AF:

0.00685

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00787

Gnomad FIN exome

AF:

0.0166

Gnomad NFE exome

AF:

0.00723

Gnomad OTH exome

AF:

0.00993

GnomAD4 exome

AF:

0.00724

AC:

10585

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00729

AC XY:

5301

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00425

Gnomad4 ASJ exome

AF:

0.00624

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00820

Gnomad4 FIN exome

AF:

0.0162

Gnomad4 NFE exome

AF:

0.00729

Gnomad4 OTH exome

AF:

0.00695

GnomAD4 genome

AF:

0.00519

AC:

791

AN:

152266

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

411

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00321

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00621

Gnomad4 FIN

AF:

0.0156

Gnomad4 NFE

AF:

0.00656

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00690

Hom.:

Bravo

AF:

0.00459

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00640

AC:

ExAC

AF:

0.00696

AC:

845

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00829

EpiControl

AF:

0.00676

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

0.051

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

5.1

DANN

Benign

0.87

DEOGEN2

Benign

0.0053

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.32

.;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Uncertain

0.042

MutationAssessor

Benign

-1.2

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.23

Sift

Benign

0.57

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.0

B;B

Vest4

0.021

MVP

0.092

MPC

0.088

ClinPred

0.00031

GERP RS

2.0

Varity_R

0.072

gMVP

0.085

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