10-92893405-C-T

Variant names:

• chr10-92893405-C-T
• NM_019053.6:c.158C>T
• EXOC6 p.Ala53Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019053.6(EXOC6):​c.158C>T​(p.Ala53Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EXOC6 NM_019053.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2562515).

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.158C>T	p.Ala53Val	missense	Exon 2 of 22	NP_061926.3
	EXOC6	NM_001319194.2		c.206C>T	p.Ala69Val	missense	Exon 3 of 23	NP_001306123.1
	EXOC6	NM_001319195.2		c.158C>T	p.Ala53Val	missense	Exon 2 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.158C>T	p.Ala53Val	missense	Exon 2 of 22	ENSP00000260762.6	Q8TAG9-1
	EXOC6	ENST00000443748.6	TSL:1	c.158C>T	p.Ala53Val	missense	Exon 2 of 18	ENSP00000396206.2	E7EW84
	EXOC6	ENST00000371552.8	TSL:5	c.143C>T	p.Ala48Val	missense	Exon 2 of 22	ENSP00000360607.4	Q8TAG9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.060
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		5.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.079
Sift	Benign	0.22	T
Sift4G	Benign	0.28	T
Varity_R		0.27
gMVP		0.43
Mutation Taster		=65/35	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-94653162;