Variant 16-67185149-T-C 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_178516.4(EXOC3L1):c.1736A>G(p.Asn579Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,613,032 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

EXOC3L1
NM_178516.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.103

Variant links:

Genes affected

EXOC3L1 (HGNC:27540): (exocyst complex component 3 like 1) Predicted to enable SNARE binding activity. Predicted to be involved in exocyst localization; exocytosis; and peptide hormone secretion. Predicted to be located in secretory granule. Predicted to be part of exocyst. [provided by Alliance of Genome Resources, Apr 2022]

EXOC3L1 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=0.022942245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC3L1	NM_178516.4 linkuse as main transcript	c.1736A>G	p.Asn579Ser	missense_variant	11/14	ENST00000314586.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC3L1	ENST00000314586.11 linkuse as main transcript	c.1736A>G	p.Asn579Ser	missense_variant	11/14	2	NM_178516.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00124

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000548

AC:

136

AN:

248304

Hom.:

AF XY:

0.000489

AC XY:

AN XY:

134926

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.0000869

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:

0.00112

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.00121

AC:

1772

AN:

1460962

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

861

AN XY:

726772

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000571

Gnomad4 NFE exome

AF:

0.00156

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.000664

AC:

101

AN:

152070

Hom.:

Cov.:

AF XY:

0.000619

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00124

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.00102

Hom.:

Bravo

AF:

0.000688

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000585

AC:

EpiCase

AF:

0.00115

EpiControl

AF:

0.00136

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

Sep 17, 2021

The c.1736A>G (p.N579S) alteration is located in exon 11 (coding exon 10) of the EXOC3L1 gene. This alteration results from a A to G substitution at nucleotide position 1736, causing the asparagine (N) at amino acid position 579 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

0.076

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.00041

T;.;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.023

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.98

L;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.31

N;N;N

REVEL

Benign

0.026

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.19

T;.;T

Polyphen

0.0030

B;B;.

Vest4

0.076

MVP

0.28

MPC

0.69

ClinPred

0.0038

GERP RS

2.3

Varity_R

0.037

gMVP

0.050

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