10-92893405-C-T

Position:

• chr10-92893405-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC6	NM_019053.6	c.158C>T	p.Ala53Val	missense_variant	2/22	ENST00000260762.10	NP_061926.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC6	ENST00000260762.10	c.158C>T	p.Ala53Val	missense_variant	2/22	1	NM_019053.6	ENSP00000260762	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.158C>T (p.A53V) alteration is located in exon 2 (coding exon 2) of the EXOC6 gene. This alteration results from a C to T substitution at nucleotide position 158, causing the alanine (A) at amino acid position 53 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Benign	0.060
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;T;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.079
Sift	Benign	0.22	T;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.52, 0.048	.;P;.;B
Vest4		0.41
MVP		0.40
MPC		0.23
ClinPred		0.78	D
GERP RS		5.2
Varity_R		0.27
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-94653162;