rs11187215

chr10-92911092-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.663+1461A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 136,400 control chromosomes in the GnomAD database, including 868 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 0.11 (868 hom., cov: 32)
• Consequence: EXOC6 NM_019053.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC6	NM_019053.6	c.663+1461A>G		intron_variant		ENST00000260762.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC6	ENST00000260762.10	c.663+1461A>G		intron_variant		1	NM_019053.6	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 15469 AN: 136286 Hom.: 866 Cov.: 32

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0279

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.114 AC: 15491 AN: 136400 Hom.: 868 Cov.: 32 AF XY: 0.114 AC XY: 7624 AN XY: 66594

Gnomad4 AFR AF: 0.0762

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0277

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.114

Alfa AF: 0.114 Hom.: 1360

Bravo AF: 0.106

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.8
Dann	Benign	0.68

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: rs11187215; hg19: chr10-94670849;