Variant 14-103102316-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077594.2(EXOC3L4):c.593G>T(p.Arg198Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000829 in 1,567,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

EXOC3L4
NM_001077594.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.102

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22809124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC3L4	NM_001077594.2 linkuse as main transcript	c.593G>T	p.Arg198Leu	missense_variant	3/12	ENST00000688303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EXOC3L4	ENST00000688303.1 linkuse as main transcript	c.593G>T	p.Arg198Leu	missense_variant	3/12		NM_001077594.2	P1
EXOC3L4	ENST00000380069.7 linkuse as main transcript	c.593G>T	p.Arg198Leu	missense_variant	2/11	1		P1
EXOC3L4	ENST00000687959.1 linkuse as main transcript	c.593G>T	p.Arg198Leu	missense_variant	4/13			P1
EXOC3L4	ENST00000559116.1 linkuse as main transcript	c.287-1625G>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000636

AC:

AN:

1414958

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000263

Gnomad4 NFE exome

AF:

0.00000548

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

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

May 18, 2022

The c.593G>T (p.R198L) alteration is located in exon 2 (coding exon 2) of the EXOC3L4 gene. This alteration results from a G to T substitution at nucleotide position 593, causing the arginine (R) at amino acid position 198 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.59

M_CAP

Benign

0.014

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

0.78

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.054

Sift

Uncertain

0.026

Sift4G

Benign

0.15

Polyphen

0.82

Vest4

0.18

MutPred

0.62

Gain of catalytic residue at R198 (P = 0.0262);

MVP

0.23

MPC

0.044

ClinPred

0.73

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.30

gMVP

0.38

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