16-67187147-A-G

Position:

• chr16-67187147-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.1041-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.978 in 1,612,662 control chromosomes in the GnomAD database, including 772,091 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.98 (73629 hom., cov: 31)
  • Exomes 𝑓: 0.98 (698462 hom.)
• Consequence: EXOC3L1 NM_178516.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0006197
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.993

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC3L1	NM_178516.4	c.1041-9T>C		splice_polypyrimidine_tract_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.1041-9T>C		splice_polypyrimidine_tract_variant, intron_variant		2	NM_178516.4	ENSP00000325674	P1

Frequencies

GnomAD3 genomes AF: 0.983 AC: 149593 AN: 152134 Hom.: 73574 Cov.: 31

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.974

Gnomad OTH AF: 0.973

GnomAD3 exomes AF: 0.983 AC: 246131 AN: 250270 Hom.: 121060 AF XY: 0.983 AC XY: 133119 AN XY: 135416

Gnomad AFR exome AF: 0.996

Gnomad AMR exome AF: 0.985

Gnomad ASJ exome AF: 0.976

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.995

Gnomad FIN exome AF: 0.993

Gnomad NFE exome AF: 0.975

Gnomad OTH exome AF: 0.974

GnomAD4 exome AF: 0.978 AC: 1428209 AN: 1460410 Hom.: 698462 Cov.: 62 AF XY: 0.978 AC XY: 710661 AN XY: 726514

Gnomad4 AFR exome AF: 0.996

Gnomad4 AMR exome AF: 0.983

Gnomad4 ASJ exome AF: 0.975

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.994

Gnomad4 FIN exome AF: 0.991

Gnomad4 NFE exome AF: 0.975

Gnomad4 OTH exome AF: 0.977

GnomAD4 genome AF: 0.983 AC: 149707 AN: 152252 Hom.: 73629 Cov.: 31 AF XY: 0.984 AC XY: 73222 AN XY: 74440

Gnomad4 AFR AF: 0.995

Gnomad4 AMR AF: 0.978

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.991

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.974

Gnomad4 OTH AF: 0.973

Alfa AF: 0.977 Hom.: 29630

Bravo AF: 0.983

Asia WGS AF: 0.994 AC: 3458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00062
dbscSNV1_RF	Benign	0.012
SpliceAI score (max)		0.030		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: rs9924876; hg19: chr16-67221050;