5-139188987-A-C

Variant names:

• chr5-139188987-A-C
• rs929775
• NM_022464.5:c.-11+9282T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022464.5(SIL1):​c.-11+9282T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,068 control chromosomes in the GnomAD database, including 17,877 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (17877 hom., cov: 32)
• Consequence: SIL1 NM_022464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 3 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIL1	NM_022464.5	c.-11+9282T>G		intron_variant	Intron 1 of 9	ENST00000394817.7	NP_071909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIL1	ENST00000394817.7	c.-11+9282T>G		intron_variant	Intron 1 of 9	1	NM_022464.5	ENSP00000378294.2

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72473 AN: 151950 Hom.: 17853 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.481

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 72534 AN: 152068 Hom.: 17877 Cov.: 32 AF XY: 0.476 AC XY: 35425 AN XY: 74348

African (AFR) AF: 0.430 AC: 17836 AN: 41468

American (AMR) AF: 0.426 AC: 6503 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1751 AN: 3470

East Asian (EAS) AF: 0.140 AC: 728 AN: 5182

South Asian (SAS) AF: 0.554 AC: 2672 AN: 4824

European-Finnish (FIN) AF: 0.540 AC: 5710 AN: 10566

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35772 AN: 67970

Other (OTH) AF: 0.478 AC: 1009 AN: 2110

Alfa AF: 0.479 Hom.: 7483

Bravo AF: 0.461

Asia WGS AF: 0.350 AC: 1222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.73
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs929775; hg19: chr5-138524676;