Variant 16-67186596-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_178516.4(EXOC3L1):c.1346A>G(p.His449Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00532 in 1,614,112 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 64 hom. )

Consequence

EXOC3L1
NM_178516.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.829

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 -6 ACMG points.

BP6

Variant 16-67186596-T-C is Benign according to our data. Variant chr16-67186596-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2646611.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC3L1	NM_178516.4 linkuse as main transcript	c.1346A>G	p.His449Arg	missense_variant	8/14	ENST00000314586.11	NP_848611.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
EXOC3L1	ENST00000314586.11 linkuse as main transcript	c.1346A>G	p.His449Arg	missense_variant	8/14	2	NM_178516.4	ENSP00000325674	P1
EXOC3L1	ENST00000563889.1 linkuse as main transcript	c.1052A>G	p.His351Arg	missense_variant	7/12	2		ENSP00000455223
EXOC3L1	ENST00000545725.6 linkuse as main transcript	c.1037A>G	p.His346Arg	missense_variant	7/12	2		ENSP00000439910
EXOC3L1	ENST00000564324.5 linkuse as main transcript	c.*270A>G		3_prime_UTR_variant, NMD_transcript_variant	5/11	2		ENSP00000456435

Frequencies

GnomAD3 genomes

AF:

0.00415

AC:

631

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00248

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00581

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00532

AC:

1336

AN:

251364

Hom.:

AF XY:

0.00561

AC XY:

762

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.0271

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00728

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00631

Gnomad OTH exome

AF:

0.00620

GnomAD4 exome

AF:

0.00544

AC:

7953

AN:

1461778

Hom.:

Cov.:

AF XY:

0.00561

AC XY:

4081

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.0308

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00670

Gnomad4 FIN exome

AF:

0.000711

Gnomad4 NFE exome

AF:

0.00542

Gnomad4 OTH exome

AF:

0.00603

GnomAD4 genome

AF:

0.00414

AC:

631

AN:

152334

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

276

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.00581

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00604

Hom.:

Bravo

AF:

0.00424

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.00756

AC:

ExAC

AF:

0.00516

AC:

626

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00600

EpiControl

AF:

0.00717

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

EXOC3L1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.00087

T;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.53

T;T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.080

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.34

T;T;T

Sift4G

Uncertain

0.024

D;.;T

Polyphen

0.036

B;B;.

Vest4

0.41

MVP

0.46

MPC

0.056

ClinPred

0.0085

GERP RS

4.4

Varity_R

0.091

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.51

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.51

Position offset: 5

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