Variant rs2297067 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001077594.2(EXOC3L4):c.229C>T(p.Arg77Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,612,946 control chromosomes in the GnomAD database, including 46,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.20 ( 3495 hom., cov: 33)

Exomes 𝑓: 0.24 ( 42629 hom. )

Consequence

EXOC3L4
NM_001077594.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.470

Variant links:

Genes affected

EXOC3L4 (HGNC:20120): (exocyst complex component 3 like 4) Predicted to enable SNARE binding activity. Predicted to be involved in exocyst localization and exocytosis. Predicted to be part of exocyst. [provided by Alliance of Genome Resources, Apr 2022]

EXOC3L4 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=0.0054156184).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC3L4	NM_001077594.2 linkuse as main transcript	c.229C>T	p.Arg77Trp	missense_variant	2/12	ENST00000688303.1	NP_001071062.1	Q17RC7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EXOC3L4	ENST00000688303.1 linkuse as main transcript	c.229C>T	p.Arg77Trp	missense_variant	2/12		NM_001077594.2	ENSP00000509130.1	Q17RC7
EXOC3L4	ENST00000380069.7 linkuse as main transcript	c.229C>T	p.Arg77Trp	missense_variant	1/11	1		ENSP00000369409.3	Q17RC7
EXOC3L4	ENST00000687959.1 linkuse as main transcript	c.229C>T	p.Arg77Trp	missense_variant	3/13			ENSP00000508483.1	Q17RC7
EXOC3L4	ENST00000559116.1 linkuse as main transcript	c.121C>T	p.Arg41Trp	missense_variant	1/3	5		ENSP00000454163.1	H0YNV0

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30638

AN:

152136

Hom.:

3488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.241

Gnomad OTH

AF:

0.228

GnomAD3 exomes

AF:

0.224

AC:

55862

AN:

248846

Hom.:

6577

AF XY:

0.231

AC XY:

31148

AN XY:

134842

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.252

Gnomad SAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.221

Gnomad NFE exome

AF:

0.241

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.239

AC:

349792

AN:

1460692

Hom.:

42629

Cov.:

AF XY:

0.241

AC XY:

175257

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.243

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.226

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.239

GnomAD4 genome

AF:

0.201

AC:

30655

AN:

152254

Hom.:

3495

Cov.:

AF XY:

0.200

AC XY:

14918

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.112

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.253

Gnomad4 SAS

AF:

0.270

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.241

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.235

Hom.:

9475

Bravo

AF:

0.196

TwinsUK

AF:

0.249

AC:

925

ALSPAC

AF:

0.247

AC:

951

ESP6500AA

AF:

0.118

AC:

519

ESP6500EA

AF:

0.244

AC:

2098

ExAC

AF:

0.226

AC:

27453

Asia WGS

AF:

0.267

AC:

930

AN:

3478

EpiCase

AF:

0.246

EpiControl

AF:

0.249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.097

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.064

Sift

Uncertain

0.027

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;.

Vest4

0.081

MPC

0.24

ClinPred

0.058

GERP RS

-6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.094

gMVP

0.24

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