rs10045761

Variant names:

• chr5-139061600-G-A
• rs10045761
• NM_022464.5:c.245-10554C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-139061600-G-A
• chr5-139061600-G-C

Variant summary

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

The NM_022464.5(SIL1):​c.245-10554C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,068 control chromosomes in the GnomAD database, including 14,574 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 0.42 (14574 hom., cov: 32)
• Consequence: SIL1 NM_022464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650
• Publications: 2 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: Orphanet, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 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.245-10554C>T		intron	N/A	NP_071909.1	Q9H173
	SIL1	NM_001037633.2		c.245-10554C>T		intron	N/A	NP_001032722.1	Q9H173

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIL1	ENST00000394817.7	TSL:1 MANE Select	c.245-10554C>T		intron	N/A	ENSP00000378294.2	Q9H173
	SIL1	ENST00000868003.1		c.245-10554C>T		intron	N/A	ENSP00000538062.1
	SIL1	ENST00000868009.1		c.242-10554C>T		intron	N/A	ENSP00000538068.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64368 AN: 151950 Hom.: 14546 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.424 AC: 64441 AN: 152068 Hom.: 14574 Cov.: 32 AF XY: 0.419 AC XY: 31139 AN XY: 74328

African (AFR) AF: 0.598 AC: 24797 AN: 41458

American (AMR) AF: 0.349 AC: 5329 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1487 AN: 3472

East Asian (EAS) AF: 0.145 AC: 750 AN: 5180

South Asian (SAS) AF: 0.351 AC: 1692 AN: 4818

European-Finnish (FIN) AF: 0.367 AC: 3869 AN: 10556

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.372 AC: 25256 AN: 67978

Other (OTH) AF: 0.390 AC: 824 AN: 2114

Alfa AF: 0.325 Hom.: 1241

Bravo AF: 0.427

Asia WGS AF: 0.276 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.6
DANN	Benign	0.86
PhyloP100		-0.65
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: rs10045761; hg19: chr5-138397289;