Variant 14-103100380-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.161G>A(p.Arg54Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,456,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

EXOC3L4
NM_001077594.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.211

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 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=0.033641398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC3L4	NM_001077594.2 linkuse as main transcript	c.161G>A	p.Arg54Lys	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.161G>A	p.Arg54Lys	missense_variant	2/12		NM_001077594.2	ENSP00000509130.1	Q17RC7
EXOC3L4	ENST00000380069.7 linkuse as main transcript	c.161G>A	p.Arg54Lys	missense_variant	1/11	1		ENSP00000369409.3	Q17RC7
EXOC3L4	ENST00000687959.1 linkuse as main transcript	c.161G>A	p.Arg54Lys	missense_variant	3/13			ENSP00000508483.1	Q17RC7
EXOC3L4	ENST00000559116.1 linkuse as main transcript	c.53G>A	p.Arg18Lys	missense_variant	1/3	5		ENSP00000454163.1	H0YNV0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1456444

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.00

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

May 29, 2024

The c.161G>A (p.R54K) alteration is located in exon 1 (coding exon 1) of the EXOC3L4 gene. This alteration results from a G to A substitution at nucleotide position 161, causing the arginine (R) at amino acid position 54 to be replaced by a lysine (K). 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

0.099

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.2

DANN

Benign

0.84

DEOGEN2

Benign

0.00033

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.41

N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.0090

Sift

Benign

0.89

T;T

Sift4G

Benign

0.81

T;T

Polyphen

0.0

B;.

Vest4

0.034

MutPred

0.27

Gain of ubiquitination at R54 (P = 0.0337);.;

MVP

0.014

MPC

0.035

ClinPred

0.061

GERP RS

-0.42

Varity_R

0.042

gMVP

0.19

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