rs3736936

Variant names:

• chr10-93013910-G-A
• rs3736936
• NM_019053.6:c.2096-284G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-93013910-G-A
• chr10-93013910-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001319194.2(EXOC6):​c.2144-284G>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_001319194.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319194.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC6	NM_019053.6	MANE Select	c.2096-284G>A		intron	N/A	NP_061926.3
	EXOC6	NM_001319194.2		c.2144-284G>A		intron	N/A	NP_001306123.1
	EXOC6	NM_001319195.2		c.2093-284G>A		intron	N/A	NP_001306124.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC6	ENST00000260762.10	TSL:1 MANE Select	c.2096-284G>A		intron	N/A	ENSP00000260762.6
	EXOC6	ENST00000443748.6	TSL:1	c.1787-284G>A		intron	N/A	ENSP00000396206.2
	EXOC6	ENST00000371552.8	TSL:5	c.2081-284G>A		intron	N/A	ENSP00000360607.4

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

African (AFR) AF: 0.243 AC: 10078 AN: 41502

American (AMR) AF: 0.288 AC: 4397 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1157 AN: 3468

East Asian (EAS) AF: 0.770 AC: 3980 AN: 5166

South Asian (SAS) AF: 0.480 AC: 2312 AN: 4814

European-Finnish (FIN) AF: 0.280 AC: 2964 AN: 10570

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19248 AN: 67982

Other (OTH) AF: 0.287 AC: 604 AN: 2108

Alfa AF: 0.288 Hom.: 11474

Bravo AF: 0.291

Asia WGS AF: 0.591 AC: 2049 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.68
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3736936; hg19: chr10-94773667;