Variant 16-67184924-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_178516.4(EXOC3L1):c.1883T>C(p.Leu628Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

EXOC3L1
NM_178516.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC3L1	NM_178516.4 linkuse as main transcript	c.1883T>C	p.Leu628Pro	missense_variant	12/14	ENST00000314586.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC3L1	ENST00000314586.11 linkuse as main transcript	c.1883T>C	p.Leu628Pro	missense_variant	12/14	2	NM_178516.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245064

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

0.00000274

AC:

AN:

1459960

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726308

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Dec 19, 2023

The c.1883T>C (p.L628P) alteration is located in exon 12 (coding exon 11) of the EXOC3L1 gene. This alteration results from a T to C substitution at nucleotide position 1883, causing the leucine (L) at amino acid position 628 to be replaced by a proline (P). 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

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

T;.;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.6

D;D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0020

D;D;D

Sift4G

Pathogenic

0.0

D;.;D

Polyphen

1.0

D;D;.

Vest4

0.90

MutPred

0.92

Gain of disorder (P = 0.021);.;.;

MVP

0.65

MPC

2.2

ClinPred

0.99

GERP RS

4.8

Varity_R

0.95

gMVP

0.91

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