rs368666457

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7

The NM_022464.5(SIL1):c.984C>T(p.Leu328Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000277 in 1,608,820 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

SIL1
NM_022464.5 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 0.330

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 5-138951216-G-A is Benign according to our data. Variant chr5-138951216-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 199168.

BP7

Synonymous conserved (PhyloP=0.33 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIL1	NM_022464.5 link	c.984C>T	p.Leu328Leu	synonymous_variant	Exon 9 of 10	ENST00000394817.7	NP_071909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SIL1	ENST00000394817.7 link	c.984C>T	p.Leu328Leu	synonymous_variant	Exon 9 of 10	1	NM_022464.5	ENSP00000378294.2
SIL1	ENST00000509534.5 link	c.1005C>T	p.Leu335Leu	synonymous_variant	Exon 10 of 11	5		ENSP00000426858.1
SIL1	ENST00000265195.9 link	c.984C>T	p.Leu328Leu	synonymous_variant	Exon 10 of 11	5		ENSP00000265195.5
SIL1	ENST00000515008.1 link	n.319C>T		non_coding_transcript_exon_variant	Exon 3 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000485

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000273

AC:

AN:

238252

AF XY:

0.000310

show subpopulations

Gnomad AFR exome

AF:

0.0000671

Gnomad AMR exome

AF:

0.000148

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000438

Gnomad OTH exome

AF:

0.000343

GnomAD4 exome

AF:

0.000279

AC:

406

AN:

1456608

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

216

AN XY:

723954

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33374

American (AMR)

AF:

0.000158

AC:

AN:

44318

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26016

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39496

South Asian (SAS)

AF:

0.000518

AC:

AN:

84972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52850

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000296

AC:

329

AN:

1109624

Other (OTH)

AF:

0.000282

AC:

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000263

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41458

American (AMR)

AF:

0.000131

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68040

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000444

Hom.:

Bravo

AF:

0.000295

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Nov 23, 2014

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Oct 16, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Dec 05, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Marinesco-Sjögren syndrome

Benign:1

Nov 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.42

CADD

Benign

9.9

(source)

DANN

Benign

0.40

PhyloP100

0.33

Mutation Taster

=30/70

disease causing

(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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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