rs868213

Positions:

• chr16-67186554-A-G

Variant summary

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

The NM_178516.4(EXOC3L1):​c.1385+3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 1,613,062 control chromosomes in the GnomAD database, including 12,459 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (4291 hom., cov: 33)
  • Exomes 𝑓: 0.083 (8168 hom.)
• Consequence: EXOC3L1 NM_178516.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001752
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464

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 (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC3L1	NM_178516.4	c.1385+3T>C		splice_region_variant, intron_variant		ENST00000314586.11	NP_848611.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC3L1	ENST00000314586.11	c.1385+3T>C		splice_region_variant, intron_variant		2	NM_178516.4	ENSP00000325674.6
EXOC3L1	ENST00000563889.1	c.1091+3T>C		splice_region_variant, intron_variant		2		ENSP00000455223.1
EXOC3L1	ENST00000545725.6	c.1076+3T>C		splice_region_variant, intron_variant		2		ENSP00000439910.2
EXOC3L1	ENST00000564324.5	n.*309+3T>C		splice_region_variant, intron_variant		2		ENSP00000456435.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26522 AN: 152052 Hom.: 4281 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0667

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.108 AC: 27100 AN: 251068 Hom.: 2686 AF XY: 0.105 AC XY: 14204 AN XY: 135704

Gnomad AFR exome AF: 0.440

Gnomad AMR exome AF: 0.0804

Gnomad ASJ exome AF: 0.0353

Gnomad EAS exome AF: 0.0178

Gnomad SAS exome AF: 0.178

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.0716

Gnomad OTH exome AF: 0.0750

GnomAD4 exome AF: 0.0832 AC: 121596 AN: 1460892 Hom.: 8168 Cov.: 32 AF XY: 0.0843 AC XY: 61267 AN XY: 726714

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.0816

Gnomad4 ASJ exome AF: 0.0360

Gnomad4 EAS exome AF: 0.0188

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0676

Gnomad4 OTH exome AF: 0.0921

GnomAD4 genome AF: 0.175 AC: 26570 AN: 152170 Hom.: 4291 Cov.: 33 AF XY: 0.175 AC XY: 12996 AN XY: 74406

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.0942

Gnomad4 ASJ AF: 0.0303

Gnomad4 EAS AF: 0.0208

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0667

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0890 Hom.: 1889

Bravo AF: 0.181

Asia WGS AF: 0.132 AC: 459 AN: 3478

EpiCase AF: 0.0674

EpiControl AF: 0.0676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.9
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.11		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: rs868213; hg19: chr16-67220457;