chr5-139042679-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022464.5(SIL1):c.394A>C(p.Lys132Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00445 in 1,609,628 control chromosomes in the GnomAD database, including 243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 130 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 113 hom. )

Consequence

SIL1
NM_022464.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.73

Publications

6 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: Orphanet, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen

SIL1 links:

ENSG00000249593 (HGNC:):

ENSG00000249593 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022770166).

BP6

Variant 5-139042679-T-G is Benign according to our data. Variant chr5-139042679-T-G is described in ClinVar as Benign. ClinVar VariationId is 261601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022464.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIL1	NM_022464.5	MANE Select	c.394A>C	p.Lys132Gln	missense	Exon 5 of 10	NP_071909.1	Q9H173
	SIL1	NM_001037633.2		c.394A>C	p.Lys132Gln	missense	Exon 6 of 11	NP_001032722.1	Q9H173

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIL1	ENST00000394817.7	TSL:1 MANE Select	c.394A>C	p.Lys132Gln	missense	Exon 5 of 10	ENSP00000378294.2	Q9H173
SIL1	ENST00000505945.1	TSL:1	c.4A>C	p.Lys2Gln	missense	Exon 1 of 3	ENSP00000425136.1	A0RZB6
SIL1	ENST00000868003.1		c.394A>C	p.Lys132Gln	missense	Exon 5 of 11	ENSP00000538062.1

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3545

AN:

152032

Hom.:

129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0806

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00871

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0220

GnomAD2 exomes

AF:

0.00611

AC:

1536

AN:

251454

AF XY:

0.00452

show subpopulations

Gnomad AFR exome

AF:

0.0802

Gnomad AMR exome

AF:

0.00477

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00247

AC:

3605

AN:

1457478

Hom.:

113

Cov.:

AF XY:

0.00218

AC XY:

1581

AN XY:

725296

show subpopulations

African (AFR)

AF:

0.0766

AC:

2558

AN:

33400

American (AMR)

AF:

0.00546

AC:

244

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.000313

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00608

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000308

AC:

341

AN:

1108044

Other (OTH)

AF:

0.00661

AC:

398

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

186

372

557

743

929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.0234

AC:

3564

AN:

152150

Hom.:

130

Cov.:

AF XY:

0.0227

AC XY:

1686

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0809

AC:

3355

AN:

41482

American (AMR)

AF:

0.00870

AC:

133

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000416

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

67996

Other (OTH)

AF:

0.0218

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

154

309

463

618

772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00811

Hom.:

136

Bravo

AF:

0.0256

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0769

AC:

339

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00730

AC:

886

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Marinesco-Sjögren syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0023

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.7

PhyloP100

3.7

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.32

Sift

Uncertain

0.029

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.42

MVP

0.75

MPC

0.90

ClinPred

0.019

GERP RS

5.0

PromoterAI

-0.016

Neutral

(source)

Varity_R

0.48

gMVP

0.55

Mutation Taster

=89/11

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over