Variant 14-103102612-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001077594.2(EXOC3L4):c.889G>A(p.Val297Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 1,499,942 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 190 hom., cov: 34)

Exomes 𝑓: 0.0026 ( 162 hom. )

Consequence

EXOC3L4
NM_001077594.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.62

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018511713).

BP6

Variant 14-103102612-G-A is Benign according to our data. Variant chr14-103102612-G-A is described in ClinVar as [Benign]. Clinvar id is 1266695.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC3L4	NM_001077594.2 linkuse as main transcript	c.889G>A	p.Val297Met	missense_variant	3/12	ENST00000688303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC3L4	ENST00000688303.1 linkuse as main transcript	c.889G>A	p.Val297Met	missense_variant	3/12		NM_001077594.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

4121

AN:

152212

Hom.:

189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0952

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00752

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.00353

AC:

351

AN:

99326

Hom.:

AF XY:

0.00276

AC XY:

153

AN XY:

55368

show subpopulations

Gnomad AFR exome

AF:

0.0970

Gnomad AMR exome

AF:

0.00467

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00344

GnomAD4 exome

AF:

0.00262

AC:

3535

AN:

1347614

Hom.:

162

Cov.:

AF XY:

0.00221

AC XY:

1468

AN XY:

664038

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.00569

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000652

Gnomad4 SAS exome

AF:

0.000242

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000678

Gnomad4 OTH exome

AF:

0.00651

GnomAD4 genome

AF:

0.0271

AC:

4124

AN:

152328

Hom.:

190

Cov.:

AF XY:

0.0261

AC XY:

1941

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0951

Gnomad4 AMR

AF:

0.00751

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.0310

ESP6500AA

AF:

0.0667

AC:

257

ESP6500EA

AF:

0.000519

AC:

ExAC

AF:

0.00381

AC:

378

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2019

This variant is associated with the following publications: (PMID: 30255815) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.71

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.0059

Eigen

Benign

-0.058

Eigen_PC

Benign

-0.033

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.72

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.51

REVEL

Benign

0.053

Sift

Benign

1.0

Sift4G

Benign

0.13

Polyphen

0.76

Vest4

0.16

MVP

0.22

MPC

1.3

ClinPred

0.023

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.042

gMVP

0.22

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