rs12357515

Variant names:

• chr10-92965751-A-G
• rs12357515
• NM_019053.6:c.1774-8302A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.89).
• 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 rank	MANE	Protein	UniProt
EXOC6	NM_019053.6	c.1774-8302A>G		intron_variant	Intron 17 of 21	ENST00000260762.10	NP_061926.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC6	ENST00000260762.10	c.1774-8302A>G		intron_variant	Intron 17 of 21	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

African (AFR) AF: 0.0677 AC: 2810 AN: 41528

American (AMR) AF: 0.168 AC: 2563 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3472

East Asian (EAS) AF: 0.00926 AC: 48 AN: 5184

South Asian (SAS) AF: 0.0900 AC: 435 AN: 4832

European-Finnish (FIN) AF: 0.0894 AC: 946 AN: 10582

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6929 AN: 67988

Other (OTH) AF: 0.0993 AC: 210 AN: 2114

Alfa AF: 0.105 Hom.: 1500

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
PhyloP100		-1.7
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: rs12357515; hg19: chr10-94725508;