rs12357515

Positions:

• chr10-92965751-A-G

Variant summary

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

The NM_019053.6(EXOC6):​c.1774-8302A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 152,180 control chromosomes in the GnomAD database, including 773 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 0.095 (773 hom., cov: 32)
• Consequence: EXOC6 NM_019053.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

Genes affected

EXOC6 (HGNC:23196): (exocyst complex component 6) The protein encoded by this gene is highly similar to the Saccharomyces cerevisiae SEC15 gene product, which is essential for vesicular traffic from the Golgi apparatus to the cell surface in yeast. It is one of the components of a multiprotein complex required for exocytosis. The 5' portion of this gene and two neighboring cytochrome p450 genes are included in a deletion that results in an autosomal-dominant form of nonsyndromic optic nerve aplasia (ONA). Alternative splicing and the use of alternative promoters results in multiple transcript variants. A paralogous gene encoding a similar protein is present on chromosome 2. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC6	NM_019053.6	c.1774-8302A>G		intron_variant		ENST00000260762.10	NP_061926.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC6	ENST00000260762.10	c.1774-8302A>G		intron_variant		1	NM_019053.6	ENSP00000260762.6

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14499 AN: 152062 Hom.: 771 Cov.: 32

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00924

Gnomad SAS AF: 0.0895

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0961

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0955 AC: 14527 AN: 152180 Hom.: 773 Cov.: 32 AF XY: 0.0963 AC XY: 7161 AN XY: 74400

Gnomad4 AFR AF: 0.0677

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.00926

Gnomad4 SAS AF: 0.0900

Gnomad4 FIN AF: 0.0894

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0993

Alfa AF: 0.105 Hom.: 1153

Bravo AF: 0.101

Asia WGS AF: 0.0700 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.026
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
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

LitVar

Other links and lift over

dbSNP: rs12357515; hg19: chr10-94725508;