5-139121126-T-C

Variant names:

Variant summary

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

The NM_022464.5(SIL1):c.153A>G(p.Thr51Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,613,918 control chromosomes in the GnomAD database, including 160,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19435 hom., cov: 32)

Exomes 𝑓: 0.43 ( 140579 hom. )

Consequence

SIL1
NM_022464.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.964

Publications

31 publications found

Variant links:

Genes affected

SIL1 (HGNC:24624): (SIL1 nucleotide exchange factor) This gene encodes a resident endoplasmic reticulum (ER), N-linked glycoprotein with an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. This protein functions as a nucleotide exchange factor for another unfolded protein response protein. Mutations in this gene have been associated with Marinesco-Sjogren syndrome. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

SIL1 Gene-Disease associations (from GenCC):

Marinesco-Sjogren syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

SIL1 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=-0.81).

BP6

Variant 5-139121126-T-C is Benign according to our data. Variant chr5-139121126-T-C is described in ClinVar as Benign. ClinVar VariationId is 96085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.964 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIL1	NM_022464.5 link	c.153A>G	p.Thr51Thr	synonymous_variant	Exon 3 of 10	ENST00000394817.7	NP_071909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIL1	ENST00000394817.7 link	c.153A>G	p.Thr51Thr	synonymous_variant	Exon 3 of 10	1	NM_022464.5	ENSP00000378294.2

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74610

AN:

151980

Hom.:

19397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.668

Gnomad AMI

AF:

0.353

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.475

GnomAD2 exomes

AF:

0.427

AC:

107454

AN:

251432

AF XY:

0.423

show subpopulations

Gnomad AFR exome

AF:

0.672

Gnomad AMR exome

AF:

0.401

Gnomad ASJ exome

AF:

0.482

Gnomad EAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.461

Gnomad NFE exome

AF:

0.442

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.434

AC:

634266

AN:

1461818

Hom.:

140579

Cov.:

AF XY:

0.433

AC XY:

315159

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.678

AC:

22710

AN:

33480

American (AMR)

AF:

0.401

AC:

17913

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.487

AC:

12724

AN:

26134

East Asian (EAS)

AF:

0.194

AC:

7710

AN:

39700

South Asian (SAS)

AF:

0.388

AC:

33459

AN:

86256

European-Finnish (FIN)

AF:

0.462

AC:

24688

AN:

53394

Middle Eastern (MID)

AF:

0.472

AC:

2717

AN:

5762

European-Non Finnish (NFE)

AF:

0.437

AC:

485838

AN:

1111978

Other (OTH)

AF:

0.439

AC:

26507

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

22456

44912

67368

89824

112280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14658

29316

43974

58632

73290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.491

AC:

74699

AN:

152100

Hom.:

19435

Cov.:

AF XY:

0.485

AC XY:

36089

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.668

AC:

27719

AN:

41482

American (AMR)

AF:

0.410

AC:

6267

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

1710

AN:

3470

East Asian (EAS)

AF:

0.169

AC:

878

AN:

5188

South Asian (SAS)

AF:

0.372

AC:

1789

AN:

4814

European-Finnish (FIN)

AF:

0.454

AC:

4804

AN:

10570

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.442

AC:

30062

AN:

67970

Other (OTH)

AF:

0.474

AC:

1001

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1898

3796

5695

7593

9491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.476

Hom.:

9911

Bravo

AF:

0.494

Asia WGS

AF:

0.304

AC:

1055

AN:

3478

EpiCase

AF:

0.439

EpiControl

AF:

0.433

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Dec 27, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 05, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Marinesco-Sjögren syndrome

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Apr 14, 2017

Athena Diagnostics

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

-0.81

CADD

Benign

0.65

(source)

DANN

Benign

0.39

PhyloP100

-0.96

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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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