16-67184714-C-T

Variant names:

• chr16-67184714-C-T
• rs765757293
• NM_178516.4:c.2002G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178516.4(EXOC3L1):​c.2002G>A​(p.Gly668Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000701 in 1,426,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: EXOC3L1 NM_178516.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.05
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13653994).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178516.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC3L1	NM_178516.4	MANE Select	c.2002G>A	p.Gly668Ser	missense	Exon 13 of 14	NP_848611.2	Q86VI1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC3L1	ENST00000314586.11	TSL:2 MANE Select	c.2002G>A	p.Gly668Ser	missense	Exon 13 of 14	ENSP00000325674.6	Q86VI1
	EXOC3L1	ENST00000563889.1	TSL:2	c.1799G>A	p.Trp600*	stop_gained	Exon 11 of 12	ENSP00000455223.1	H3BPA4
	EXOC3L1	ENST00000545725.6	TSL:2	c.1784G>A	p.Trp595*	stop_gained	Exon 11 of 12	ENSP00000439910.2	F5H4W1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000136 AC: 3 AN: 220364 AF XY: 0.0000165

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000114

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000701 AC: 10 AN: 1426968 Hom.: 0 Cov.: 32 AF XY: 0.0000113 AC XY: 8 AN XY: 707356

African (AFR) AF: 0.00 AC: 0 AN: 33016

American (AMR) AF: 0.00 AC: 0 AN: 43002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24868

East Asian (EAS) AF: 0.0000763 AC: 3 AN: 39328

South Asian (SAS) AF: 0.0000597 AC: 5 AN: 83794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1098246

Other (OTH) AF: 0.0000169 AC: 1 AN: 59240

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000827 AC: 1

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.3
DANN	Benign	0.94
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.3	L
PhyloP100		-1.1
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.061
Sift	Benign	0.17	T
Sift4G	Benign	0.29	T
Polyphen		0.099	B
Vest4		0.12
MutPred		0.43		Loss of catalytic residue at A667 (P = 0.0589)
MVP		0.076
MPC		1.1
ClinPred		0.035	T
GERP RS		-3.7
Varity_R		0.052
gMVP		0.56
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs765757293; hg19: chr16-67218617; COSMIC: COSV105012655; COSMIC: COSV105012655;