rs868213

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-67186554-A-C
• chr16-67186554-A-G
• chr16-67186554-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178516.4(EXOC3L1):​c.1385+3T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,196 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EXOC3L1 NM_178516.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002446
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC3L1	NM_178516.4	c.1385+3T>G		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>G		splice_region_variant, intron_variant	Intron 8 of 13	2	NM_178516.4	ENSP00000325674.6
EXOC3L1	ENST00000563889.1	c.1091+3T>G		splice_region_variant, intron_variant	Intron 7 of 11	2		ENSP00000455223.1
EXOC3L1	ENST00000545725.6	c.1076+3T>G		splice_region_variant, intron_variant	Intron 7 of 11	2		ENSP00000439910.2
EXOC3L1	ENST00000564324.5	n.*309+3T>G		splice_region_variant, intron_variant	Intron 5 of 10	2		ENSP00000456435.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461196 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726860

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.3
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.026
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-67220457;