Variant 14-103102336-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001077594.2(EXOC3L4):c.613G>A(p.Gly205Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,410,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

EXOC3L4
NM_001077594.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.691

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:

EXOC3L4 (HGNC:):

EXOC3L4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060301423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC3L4	NM_001077594.2 linkuse as main transcript	c.613G>A	p.Gly205Ser	missense_variant	3/12	ENST00000688303.1	NP_001071062.1	Q17RC7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC3L4	ENST00000688303.1 linkuse as main transcript	c.613G>A	p.Gly205Ser	missense_variant	3/12		NM_001077594.2	ENSP00000509130.1		Q17RC7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000593

AC:

AN:

168650

Hom.:

AF XY:

0.00

AC XY:

AN XY:

93368

show subpopulations

Gnomad AFR exome

AF:

0.000110

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000284

AC:

AN:

1410852

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

698906

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2024

The c.613G>A (p.G205S) alteration is located in exon 2 (coding exon 2) of the EXOC3L4 gene. This alteration results from a G to A substitution at nucleotide position 613, causing the glycine (G) at amino acid position 205 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.00060

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.61

M_CAP

Benign

0.0083

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.94

REVEL

Benign

0.025

Sift

Benign

0.58

Sift4G

Benign

0.47

Polyphen

0.44

Vest4

0.073

MutPred

0.35

Gain of loop (P = 0.0045);

MVP

0.048

MPC

0.058

ClinPred

0.027

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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