rs6596460

Variant names:

• chr5-139078491-G-A
• rs6596460
• NM_022464.5:c.245-27445C>T

Variant summary

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

The NM_022464.5(SIL1):​c.245-27445C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,966 control chromosomes in the GnomAD database, including 8,211 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 0.33 (8211 hom., cov: 32)
• Consequence: SIL1 NM_022464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• 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, Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 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.245-27445C>T		intron	N/A	NP_071909.1	Q9H173
	SIL1	NM_001037633.2		c.245-27445C>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.245-27445C>T		intron	N/A	ENSP00000378294.2	Q9H173
	SIL1	ENST00000868003.1		c.245-27445C>T		intron	N/A	ENSP00000538062.1
	SIL1	ENST00000868009.1		c.242-27445C>T		intron	N/A	ENSP00000538068.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49802 AN: 151848 Hom.: 8215 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.328 AC: 49824 AN: 151966 Hom.: 8211 Cov.: 32 AF XY: 0.326 AC XY: 24235 AN XY: 74246

African (AFR) AF: 0.325 AC: 13473 AN: 41440

American (AMR) AF: 0.295 AC: 4502 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1336 AN: 3470

East Asian (EAS) AF: 0.143 AC: 738 AN: 5170

South Asian (SAS) AF: 0.345 AC: 1660 AN: 4810

European-Finnish (FIN) AF: 0.352 AC: 3711 AN: 10532

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23351 AN: 67954

Other (OTH) AF: 0.304 AC: 641 AN: 2108

Alfa AF: 0.343 Hom.: 1172

Bravo AF: 0.320

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.52
PhyloP100		0.15
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6596460;

hg19: chr5-138414180;