16-67186554-A-G

Variant names:

• chr16-67186554-A-G
• rs868213
• NM_178516.4:c.1385+3T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 32 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
EXOC3L1	NM_178516.4	c.1385+3T>C		splice_region_variant, intron_variant	Intron 8 of 13	ENST00000314586.11	NP_848611.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC3L1	ENST00000314586.11	c.1385+3T>C		splice_region_variant, intron_variant	Intron 8 of 13	2	NM_178516.4	ENSP00000325674.6
EXOC3L1	ENST00000563889.1	c.1091+3T>C		splice_region_variant, intron_variant	Intron 7 of 11	2		ENSP00000455223.1
EXOC3L1	ENST00000545725.6	c.1076+3T>C		splice_region_variant, intron_variant	Intron 7 of 11	2		ENSP00000439910.2
EXOC3L1	ENST00000564324.5	n.*309+3T>C		splice_region_variant, intron_variant	Intron 5 of 10	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

GnomAD2 exomes AF: 0.108 AC: 27100 AN: 251068 AF XY: 0.105

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 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

African (AFR) AF: 0.440 AC: 14714 AN: 33442

American (AMR) AF: 0.0816 AC: 3646 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 940 AN: 26130

East Asian (EAS) AF: 0.0188 AC: 748 AN: 39692

South Asian (SAS) AF: 0.168 AC: 14495 AN: 86220

European-Finnish (FIN) AF: 0.112 AC: 5957 AN: 53410

Middle Eastern (MID) AF: 0.0719 AC: 400 AN: 5560

European-Non Finnish (NFE) AF: 0.0676 AC: 75139 AN: 1111414

Other (OTH) AF: 0.0921 AC: 5557 AN: 60324

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

African (AFR) AF: 0.432 AC: 17903 AN: 41458

American (AMR) AF: 0.0942 AC: 1441 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 105 AN: 3468

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5182

South Asian (SAS) AF: 0.161 AC: 777 AN: 4824

European-Finnish (FIN) AF: 0.122 AC: 1294 AN: 10612

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0667 AC: 4538 AN: 68008

Other (OTH) AF: 0.131 AC: 277 AN: 2114

Alfa AF: 0.0977 Hom.: 2857

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
PhyloP100		0.46
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs868213; hg19: chr16-67220457;