NM_022464.5:c.153A>G

Variant names:

• chr5-139121126-T-C
• rs3088052
• NM_022464.5:c.153A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022464.5(SIL1):​c.153A>G​(p.Thr51Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,613,918 control chromosomes in the GnomAD database, including 160,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19435 hom., cov: 32)
  • Exomes 𝑓: 0.43 (140579 hom.)
• Consequence: SIL1 NM_022464.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.964
• Publications: 31 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-139121126-T-C is Benign according to our data. Variant chr5-139121126-T-C is described in ClinVar as Benign. ClinVar VariationId is 96085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.964 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 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.153A>G	p.Thr51Thr	synonymous	Exon 3 of 10	NP_071909.1	Q9H173
	SIL1	NM_001037633.2		c.153A>G	p.Thr51Thr	synonymous	Exon 4 of 11	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.153A>G	p.Thr51Thr	synonymous	Exon 3 of 10	ENSP00000378294.2	Q9H173
	SIL1	ENST00000868003.1		c.153A>G	p.Thr51Thr	synonymous	Exon 3 of 11	ENSP00000538062.1
	SIL1	ENST00000868009.1		c.150A>G	p.Thr50Thr	synonymous	Exon 3 of 11	ENSP00000538068.1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74610 AN: 151980 Hom.: 19397 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.475

GnomAD2 exomes AF: 0.427 AC: 107454 AN: 251432 AF XY: 0.423

Gnomad AFR exome AF: 0.672

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.482

Gnomad EAS exome AF: 0.167

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.442

Gnomad OTH exome AF: 0.433

GnomAD4 exome AF: 0.434 AC: 634266 AN: 1461818 Hom.: 140579 Cov.: 56 AF XY: 0.433 AC XY: 315159 AN XY: 727210

African (AFR) AF: 0.678 AC: 22710 AN: 33480

American (AMR) AF: 0.401 AC: 17913 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 12724 AN: 26134

East Asian (EAS) AF: 0.194 AC: 7710 AN: 39700

South Asian (SAS) AF: 0.388 AC: 33459 AN: 86256

European-Finnish (FIN) AF: 0.462 AC: 24688 AN: 53394

Middle Eastern (MID) AF: 0.472 AC: 2717 AN: 5762

European-Non Finnish (NFE) AF: 0.437 AC: 485838 AN: 1111978

Other (OTH) AF: 0.439 AC: 26507 AN: 60392

GnomAD4 genome AF: 0.491 AC: 74699 AN: 152100 Hom.: 19435 Cov.: 32 AF XY: 0.485 AC XY: 36089 AN XY: 74348

African (AFR) AF: 0.668 AC: 27719 AN: 41482

American (AMR) AF: 0.410 AC: 6267 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3470

East Asian (EAS) AF: 0.169 AC: 878 AN: 5188

South Asian (SAS) AF: 0.372 AC: 1789 AN: 4814

European-Finnish (FIN) AF: 0.454 AC: 4804 AN: 10570

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30062 AN: 67970

Other (OTH) AF: 0.474 AC: 1001 AN: 2114

Alfa AF: 0.476 Hom.: 9911

Bravo AF: 0.494

Asia WGS AF: 0.304 AC: 1055 AN: 3478

EpiCase AF: 0.439

EpiControl AF: 0.433

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Marinesco-Sjögren syndrome (5)
-	-	5	not specified (5)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.65
DANN	Benign	0.39
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3088052; hg19: chr5-138456815; COSMIC: COSV54530288;