Variant 7-133317322-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000253861.5(EXOC4):c.695T>C(p.Val232Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,486 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: 6.8e-7 ( 0 hom. )

Consequence

EXOC4
ENST00000253861.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81

Variant links:

Genes affected

EXOC4 (HGNC:30389): (exocyst complex component 4) The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to specific docking sites on the plasma membrane. Though best characterized in yeast, the component proteins and functions of exocyst complex have been demonstrated to be highly conserved in higher eukaryotes. At least eight components of the exocyst complex, including this protein, are found to interact with the actin cytoskeletal remodeling and vesicle transport machinery. The complex is also essential for the biogenesis of epithelial cell surface polarity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

EXOC4 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=0.41828462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC4	NM_021807.4 linkuse as main transcript	c.695T>C	p.Val232Ala	missense_variant	5/18	ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5 linkuse as main transcript	c.695T>C	p.Val232Ala	missense_variant	5/18	1	NM_021807.4	ENSP00000253861	P1	Q96A65-1
EXOC4	ENST00000462055.5 linkuse as main transcript	n.702T>C		non_coding_transcript_exon_variant	5/9	1
EXOC4	ENST00000393161.6 linkuse as main transcript	c.695T>C	p.Val232Ala	missense_variant	5/10	5		ENSP00000376868		Q96A65-2
EXOC4	ENST00000486013.5 linkuse as main transcript	n.724T>C		non_coding_transcript_exon_variant	5/10	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251362

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461486

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 03, 2023

The c.695T>C (p.V232A) alteration is located in exon 5 (coding exon 5) of the EXOC4 gene. This alteration results from a T to C substitution at nucleotide position 695, causing the valine (V) at amino acid position 232 to be replaced by an alanine (A). 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

0.19

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;T

Eigen

Benign

-0.19

Eigen_PC

Benign

0.0039

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.0031

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

0.90

D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.25

N;N

REVEL

Benign

0.12

Sift

Benign

0.081

T;T

Sift4G

Uncertain

0.010

D;T

Polyphen

0.0010

.;B

Vest4

0.53

MutPred

0.63

Gain of relative solvent accessibility (P = 0.0522);Gain of relative solvent accessibility (P = 0.0522);

MVP

0.68

MPC

0.17

ClinPred

0.42

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.41

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