Variant 1-231335731-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_175876.5(EXOC8):c.2015C>G(p.Ala672Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00181 in 1,614,116 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 32 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 17 hom. )

Consequence

EXOC8
NM_175876.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.71

Variant links:

Genes affected

EXOC8 (HGNC:24659): (exocyst complex component 8) This gene encodes a component of the exocyst complex, an evolutionarily conserved multi-protein complex that plays a critical role in vesicular trafficking and the secretory pathway by targeting post-Golgi vesicles to the plasma membrane. This protein is a target of activated Ral subfamily of GTPases and thereby regulates exocytosis by tethering vesicles to the plasma membrane. Mutations in this gene may be related to Joubert syndrome. [provided by RefSeq, Sep 2016]

EXOC8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006480545).

BP6

Variant 1-231335731-G-C is Benign according to our data. Variant chr1-231335731-G-C is described in ClinVar as [Benign]. Clinvar id is 767762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00978 (1489/152234) while in subpopulation AFR AF= 0.0348 (1443/41522). AF 95% confidence interval is 0.0333. There are 32 homozygotes in gnomad4. There are 678 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC8	NM_175876.5 link	c.2015C>G	p.Ala672Gly	missense_variant	1/1	ENST00000366645.1	NP_787072.2	Q8IYI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC8	ENST00000366645.1 link	c.2015C>G	p.Ala672Gly	missense_variant	1/1	6	NM_175876.5	ENSP00000355605.2		Q8IYI6

Frequencies

GnomAD3 genomes

AF:

0.00977

AC:

1486

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0348

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00266

AC:

668

AN:

251426

Hom.:

AF XY:

0.00185

AC XY:

251

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0373

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000984

AC:

1438

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000820

AC XY:

596

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0368

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.00978

AC:

1489

AN:

152234

Hom.:

Cov.:

AF XY:

0.00911

AC XY:

678

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0348

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.000731

Hom.:

Bravo

AF:

0.0115

ESP6500AA

AF:

0.0399

AC:

176

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00332

AC:

403

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 11, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.59

REVEL

Benign

0.27

Sift4G

Benign

0.33

Polyphen

0.084

Vest4

0.36

MVP

0.34

ClinPred

0.030

GERP RS

5.5

Varity_R

0.11

gMVP

0.14

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