16-67184488-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_178516.4(EXOC3L1):c.2147G>A(p.Arg716His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00782 in 1,522,036 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0081 (55 hom.)
• Consequence: EXOC3L1 NM_178516.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.663

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00631842).
• BP6: Variant 16-67184488-C-T is Benign according to our data. Variant chr16-67184488-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2646610.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC3L1	NM_178516.4	c.2147G>A	p.Arg716His	missense_variant	14/14	ENST00000314586.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC3L1	ENST00000314586.11	c.2147G>A	p.Arg716His	missense_variant	14/14	2	NM_178516.4	P1

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 750 AN: 152094 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.000755

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00922

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00538 AC: 649 AN: 120596 Hom.: 4 AF XY: 0.00579 AC XY: 386 AN XY: 66610

Gnomad AFR exome AF: 0.00137

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.00478

Gnomad FIN exome AF: 0.00191

Gnomad NFE exome AF: 0.00980

Gnomad OTH exome AF: 0.00322

GnomAD4 exome AF: 0.00814 AC: 11151 AN: 1369832 Hom.: 55 Cov.: 32 AF XY: 0.00812 AC XY: 5490 AN XY: 675846

Gnomad4 AFR exome AF: 0.00148

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00209

Gnomad4 EAS exome AF: 0.0000290

Gnomad4 SAS exome AF: 0.00461

Gnomad4 FIN exome AF: 0.00218

Gnomad4 NFE exome AF: 0.00955

Gnomad4 OTH exome AF: 0.00526

GnomAD4 genome AF: 0.00493 AC: 751 AN: 152204 Hom.: 1 Cov.: 33 AF XY: 0.00445 AC XY: 331 AN XY: 74398

Gnomad4 AFR AF: 0.00157

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.000755

Gnomad4 NFE AF: 0.00922

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00565 Hom.: 2

Bravo AF: 0.00490

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.00210 AC: 6

ESP6500EA AF: 0.00590 AC: 34

ExAC AF: 0.00277 AC: 130

Asia WGS AF: 0.00203 AC: 7 AN: 3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

EXOC3L1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	19
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0062	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	2.9	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.22
Sift	Benign	0.13	T
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.31
MVP		0.72
MPC		1.1
ClinPred		0.060	T
GERP RS		4.4
Varity_R		0.12
gMVP		0.66

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

Other links and lift over

dbSNP: rs201102355; hg19: chr16-67218391; COSMIC: COSV105012639; COSMIC: COSV105012639;