rs9939768

Positions:

• chr16-67185204-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178516.4(EXOC3L1):​c.1681C>G​(p.Gln561Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 1,612,996 control chromosomes in the GnomAD database, including 12,367 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (4248 hom., cov: 33)
  • Exomes 𝑓: 0.083 (8119 hom.)
• Consequence: EXOC3L1 NM_178516.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.583035E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC3L1	NM_178516.4	c.1681C>G	p.Gln561Glu	missense_variant	11/14	ENST00000314586.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC3L1	ENST00000314586.11	c.1681C>G	p.Gln561Glu	missense_variant	11/14	2	NM_178516.4	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26435 AN: 151734 Hom.: 4238 Cov.: 33

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0944

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0752

Gnomad NFE AF: 0.0667

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.108 AC: 26922 AN: 250226 Hom.: 2654 AF XY: 0.105 AC XY: 14203 AN XY: 135608

Gnomad AFR exome AF: 0.437

Gnomad AMR exome AF: 0.0803

Gnomad ASJ exome AF: 0.0355

Gnomad EAS exome AF: 0.0183

Gnomad SAS exome AF: 0.178

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.0716

Gnomad OTH exome AF: 0.0752

GnomAD4 exome AF: 0.0832 AC: 121568 AN: 1461140 Hom.: 8119 Cov.: 32 AF XY: 0.0843 AC XY: 61254 AN XY: 726874

Gnomad4 AFR exome AF: 0.438

Gnomad4 AMR exome AF: 0.0815

Gnomad4 ASJ exome AF: 0.0360

Gnomad4 EAS exome AF: 0.0190

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0676

Gnomad4 OTH exome AF: 0.0920

GnomAD4 genome AF: 0.174 AC: 26483 AN: 151856 Hom.: 4248 Cov.: 33 AF XY: 0.175 AC XY: 12954 AN XY: 74234

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.0944

Gnomad4 ASJ AF: 0.0303

Gnomad4 EAS AF: 0.0215

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0667

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0782 Hom.: 639

Bravo AF: 0.180

TwinsUK AF: 0.0672 AC: 249

ALSPAC AF: 0.0716 AC: 276

ESP6500AA AF: 0.419 AC: 1842

ESP6500EA AF: 0.0692 AC: 595

ExAC AF: 0.118 AC: 14278

Asia WGS AF: 0.132 AC: 460 AN: 3478

EpiCase AF: 0.0673

EpiControl AF: 0.0675

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.4
DANN	Benign	0.74
DEOGEN2	Benign	0.00017	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.11	T;T;T
MetaRNN	Benign	0.00066	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.69	N;.;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.4	N;N;N
REVEL	Benign	0.026
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.24	T;.;T
Polyphen		0.0	B;B;.
Vest4		0.027
MPC		0.93
ClinPred		0.00052	T
GERP RS		3.7
Varity_R		0.049
gMVP		0.064

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: rs9939768; hg19: chr16-67219107; COSMIC: COSV52045770; COSMIC: COSV52045770;