10-92894995-A-G

Variant names:

• chr10-92894995-A-G
• rs374973254
• NM_019053.6:c.387A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_019053.6(EXOC6):​c.387A>G​(p.Val129Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,610,930 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: EXOC6 NM_019053.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.715
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-92894995-A-G is Benign according to our data. Variant chr10-92894995-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2640680.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.715 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019053.6. 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.387A>G	p.Val129Val	synonymous	Exon 4 of 22	NP_061926.3
	EXOC6	NM_001319194.2		c.435A>G	p.Val145Val	synonymous	Exon 5 of 23	NP_001306123.1
	EXOC6	NM_001319195.2		c.387A>G	p.Val129Val	synonymous	Exon 4 of 22	NP_001306124.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC6	ENST00000260762.10	TSL:1 MANE Select	c.387A>G	p.Val129Val	synonymous	Exon 4 of 22	ENSP00000260762.6	Q8TAG9-1
	EXOC6	ENST00000443748.6	TSL:1	c.387A>G	p.Val129Val	synonymous	Exon 4 of 18	ENSP00000396206.2	E7EW84
	EXOC6	ENST00000371552.8	TSL:5	c.372A>G	p.Val124Val	synonymous	Exon 4 of 22	ENSP00000360607.4	Q8TAG9-2

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 53 AN: 152224 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000307 AC: 77 AN: 250460 AF XY: 0.000318

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.000895

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00195

Gnomad NFE exome AF: 0.000195

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000157 AC: 229 AN: 1458588 Hom.: 0 Cov.: 29 AF XY: 0.000152 AC XY: 110 AN XY: 725816

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.0000447 AC: 2 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.000651 AC: 17 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86182

European-Finnish (FIN) AF: 0.00131 AC: 70 AN: 53334

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5752

European-Non Finnish (NFE) AF: 0.0000929 AC: 103 AN: 1109256

Other (OTH) AF: 0.000232 AC: 14 AN: 60254

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152342 Hom.: 1 Cov.: 32 AF XY: 0.000524 AC XY: 39 AN XY: 74492

African (AFR) AF: 0.0000240 AC: 1 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68026

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000244 Hom.: 0

Bravo AF: 0.000110

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000546

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.4
DANN	Benign	0.61
PhyloP100		0.71
Mutation Taster		=96/4	polymorphism

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: rs374973254; hg19: chr10-94654752;