10-93013910-G-A

Position:

• chr10-93013910-G-A

Variant summary

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

The NM_019053.6(EXOC6):​c.2096-284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,098 control chromosomes in the GnomAD database, including 7,516 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 0.30 (7516 hom., cov: 32)
• Consequence: EXOC6 NM_019053.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC6	NM_019053.6	c.2096-284G>A		intron_variant		ENST00000260762.10	NP_061926.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC6	ENST00000260762.10	c.2096-284G>A		intron_variant		1	NM_019053.6	ENSP00000260762	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44875 AN: 151980 Hom.: 7513 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.295 AC: 44894 AN: 152098 Hom.: 7516 Cov.: 32 AF XY: 0.301 AC XY: 22357 AN XY: 74356

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.287

Alfa AF: 0.276 Hom.: 1603

Bravo AF: 0.291

Asia WGS AF: 0.591 AC: 2049 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
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: rs3736936; hg19: chr10-94773667;