chr1-231337365-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_175876.5(EXOC8):c.381G>C(p.Ala127Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,602,166 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 88 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 93 hom. )

Consequence

EXOC8
NM_175876.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.276

Publications

0 publications found

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:

SPRTN (HGNC:25356): (SprT-like N-terminal domain) The protein encoded by this gene may play a role in DNA repair during replication of damaged DNA. This protein recruits valosin containing protein (p97) to stalled DNA replication forks where it may prevent excessive translesional DNA synthesis and limit the number of DNA-damage induced mutations. It may also be involved in replication-related G2/M-checkpoint regulation. Deficiency of a similar protein in mouse causes chromosomal instability and progeroid phenotypes. Mutations in this gene have been associated with Ruijs-Aalfs syndrome (RJALS). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

SPRTN Gene-Disease associations (from GenCC):

progeroid features-hepatocellular carcinoma predisposition syndrome
Inheritance: AR Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

SPRTN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-231337365-C-G is Benign according to our data. Variant chr1-231337365-C-G is described in ClinVar as [Benign]. Clinvar id is 767763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.276 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC8	NM_175876.5 link	c.381G>C	p.Ala127Ala	synonymous_variant	Exon 1 of 1	ENST00000366645.1	NP_787072.2	Q8IYI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC8	ENST00000366645.1 link	c.381G>C	p.Ala127Ala	synonymous_variant	Exon 1 of 1	6	NM_175876.5	ENSP00000355605.2		Q8IYI6
SPRTN	ENST00000391858.8 link	c.-1019C>G		5_prime_UTR_variant	Exon 1 of 4	1		ENSP00000375731.4		Q9H040-2

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2571

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0590

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0125

GnomAD2 exomes

AF:

0.00441

AC:

1032

AN:

233768

AF XY:

0.00337

show subpopulations

Gnomad AFR exome

AF:

0.0609

Gnomad AMR exome

AF:

0.00365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000131

Gnomad OTH exome

AF:

0.00292

GnomAD4 exome

AF:

0.00186

AC:

2695

AN:

1449894

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1164

AN XY:

721716

show subpopulations

African (AFR)

AF:

0.0630

AC:

2109

AN:

33462

American (AMR)

AF:

0.00392

AC:

175

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.000279

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42408

Middle Eastern (MID)

AF:

0.00417

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000810

AC:

AN:

1111532

Other (OTH)

AF:

0.00453

AC:

273

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

176

351

527

702

878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0170

AC:

2589

AN:

152272

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1202

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0593

AC:

2463

AN:

41546

American (AMR)

AF:

0.00503

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68026

Other (OTH)

AF:

0.0123

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

120

239

359

478

598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00787

Hom.:

Bravo

AF:

0.0193

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000238

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.8

(source)

DANN

Benign

0.69

PhyloP100

0.28

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr1-231337365-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over