Variant 10-92848630-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019053.6(EXOC6):c.97C>T(p.Leu33Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000786 in 1,272,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

EXOC6
NM_019053.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

Variant links:

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]

EXOC6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32502145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC6	NM_019053.6 linkuse as main transcript	c.97C>T	p.Leu33Phe	missense_variant	1/22	ENST00000260762.10	NP_061926.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC6	ENST00000260762.10 linkuse as main transcript	c.97C>T	p.Leu33Phe	missense_variant	1/22	1	NM_019053.6	ENSP00000260762	P1	Q8TAG9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.86e-7

AC:

AN:

1272346

Hom.:

Cov.:

AF XY:

0.00000158

AC XY:

AN XY:

631680

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.98e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2023

The c.97C>T (p.L33F) alteration is located in exon 1 (coding exon 1) of the EXOC6 gene. This alteration results from a C to T substitution at nucleotide position 97, causing the leucine (L) at amino acid position 33 to be replaced by a phenylalanine (F). 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

Pathogenic

0.74

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.10

.;T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.045

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.92

D;T;D

M_CAP

Pathogenic

0.53

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;.;L

MutationTaster

Benign

1.0

D;D;D;D;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.090

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.67

T;T;T

Sift4G

Benign

0.50

T;T;T

Polyphen

0.62

P;.;B

Vest4

0.50

MutPred

0.54

Gain of phosphorylation at T32 (P = 0.1998);Gain of phosphorylation at T32 (P = 0.1998);Gain of phosphorylation at T32 (P = 0.1998);

MVP

0.45

MPC

0.28

ClinPred

0.71

GERP RS

2.9

Varity_R

0.12

gMVP

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over