Variant chr1-34795168-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002060.3(GJA4):c.955C>T(p.Pro319Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,611,582 control chromosomes in the GnomAD database, including 78,464 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.37 ( 11321 hom., cov: 31)

Exomes 𝑓: 0.30 ( 67143 hom. )

Consequence

GJA4
NM_002060.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.296

Variant links:

Genes affected

GJA4 (HGNC:4278): (gap junction protein alpha 4) This gene encodes a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Mutations in this gene have been associated with atherosclerosis and a higher risk of myocardial infarction. [provided by RefSeq, Jul 2008]

GJA4 links:

SMIM12 (HGNC:25154): (small integral membrane protein 12) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5687552E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GJA4	NM_002060.3 linkuse as main transcript	c.955C>T	p.Pro319Ser	missense_variant	2/2	ENST00000342280.5	NP_002051.2
GJA4	XM_005270750.3 linkuse as main transcript	c.955C>T	p.Pro319Ser	missense_variant	2/2		XP_005270807.1
GJA4	XM_017001043.3 linkuse as main transcript	c.955C>T	p.Pro319Ser	missense_variant	2/2		XP_016856532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJA4	ENST00000342280.5 linkuse as main transcript	c.955C>T	p.Pro319Ser	missense_variant	2/2	1	NM_002060.3	ENSP00000343676	P1
SMIM12	ENST00000426886.1 linkuse as main transcript	c.207+60603G>A		intron_variant, NMD_transcript_variant		1		ENSP00000429902

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55742

AN:

151704

Hom.:

11307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.338

GnomAD3 exomes

AF:

0.303

AC:

75790

AN:

249984

Hom.:

12611

AF XY:

0.298

AC XY:

40282

AN XY:

135242

show subpopulations

Gnomad AFR exome

AF:

0.539

Gnomad AMR exome

AF:

0.240

Gnomad ASJ exome

AF:

0.292

Gnomad EAS exome

AF:

0.172

Gnomad SAS exome

AF:

0.220

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.310

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.297

AC:

433317

AN:

1459762

Hom.:

67143

Cov.:

AF XY:

0.295

AC XY:

214362

AN XY:

726284

show subpopulations

Gnomad4 AFR exome

AF:

0.541

Gnomad4 AMR exome

AF:

0.244

Gnomad4 ASJ exome

AF:

0.290

Gnomad4 EAS exome

AF:

0.181

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.431

Gnomad4 NFE exome

AF:

0.295

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.367

AC:

55785

AN:

151820

Hom.:

11321

Cov.:

AF XY:

0.367

AC XY:

27189

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.540

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.177

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.430

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.306

Hom.:

10290

Bravo

AF:

0.362

TwinsUK

AF:

0.289

AC:

1071

ALSPAC

AF:

0.285

AC:

1100

ESP6500AA

AF:

0.525

AC:

2315

ESP6500EA

AF:

0.303

AC:

2603

ExAC

AF:

0.310

AC:

37594

Asia WGS

AF:

0.226

AC:

786

AN:

3478

EpiCase

AF:

0.307

EpiControl

AF:

0.303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.68

DANN

Benign

0.54

DEOGEN2

Benign

0.025

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.19

MetaRNN

Benign

0.000016

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.58

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.34

REVEL

Benign

0.24

Sift

Benign

0.80

Sift4G

Benign

0.25

Polyphen

0.0

Vest4

0.021

MPC

0.49

ClinPred

0.00026

GERP RS

0.013

Varity_R

0.028

gMVP

0.42

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over