Genetic Variant EXOC3:p.Ser42Ser (chr5-446331-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_007277.5(EXOC3):c.126C>T(p.Ser42Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00792 in 1,608,386 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 39 hom., cov: 33)

Exomes 𝑓: 0.0072 ( 89 hom. )

Consequence

EXOC3
NM_007277.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.38

Variant links:

Genes affected

EXOC3 (HGNC:30378): (exocyst complex component 3) 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. [provided by RefSeq, Jul 2008]

EXOC3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 5-446331-C-T is Benign according to our data. Variant chr5-446331-C-T is described in ClinVar as [Benign]. Clinvar id is 778863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.38 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0152 (2314/152280) while in subpopulation AFR AF= 0.0411 (1708/41542). AF 95% confidence interval is 0.0395. There are 39 homozygotes in gnomad4. There are 1090 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC3	NM_007277.5 link	c.126C>T	p.Ser42Ser	synonymous_variant	Exon 2 of 13	ENST00000512944.6	NP_009208.2	O60645A0A024QYZ6Q69YP2
EXOC3	XM_047416683.1 link	c.126C>T	p.Ser42Ser	synonymous_variant	Exon 2 of 7		XP_047272639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC3	ENST00000512944.6 link	c.126C>T	p.Ser42Ser	synonymous_variant	Exon 2 of 13	1	NM_007277.5	ENSP00000425587.1		O60645

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

2313

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0412

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00591

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00759

AC:

1840

AN:

242488

Hom.:

AF XY:

0.00749

AC XY:

986

AN XY:

131662

show subpopulations

Gnomad AFR exome

AF:

0.0449

Gnomad AMR exome

AF:

0.00376

Gnomad ASJ exome

AF:

0.000420

Gnomad EAS exome

AF:

0.000225

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.000712

Gnomad NFE exome

AF:

0.00554

Gnomad OTH exome

AF:

0.00582

GnomAD4 exome

AF:

0.00716

AC:

10423

AN:

1456106

Hom.:

Cov.:

AF XY:

0.00713

AC XY:

5160

AN XY:

724070

show subpopulations

Gnomad4 AFR exome

AF:

0.0436

Gnomad4 AMR exome

AF:

0.00415

Gnomad4 ASJ exome

AF:

0.000545

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0134

Gnomad4 FIN exome

AF:

0.000885

Gnomad4 NFE exome

AF:

0.00643

Gnomad4 OTH exome

AF:

0.00687

GnomAD4 genome

AF:

0.0152

AC:

2314

AN:

152280

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1090

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0411

Gnomad4 AMR

AF:

0.00627

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00591

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00988

Hom.:

Bravo

AF:

0.0181

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.0

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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