rs35080367

Variant names:

• chr5-138951300-G-A
• rs35080367
• NM_022464.5:c.900C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-138951300-G-A
• chr5-138951300-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_022464.5(SIL1):​c.900C>T​(p.Phe300Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000668 in 1,564,220 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00034 (5 hom.)
• Consequence: SIL1 NM_022464.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.62
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 5-138951300-G-A is Benign according to our data. Variant chr5-138951300-G-A is described in ClinVar as Benign. ClinVar VariationId is 261602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.62 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00372 (567/152376) while in subpopulation AFR AF = 0.0128 (534/41600). AF 95% confidence interval is 0.0119. There are 3 homozygotes in GnomAd4. There are 294 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.900C>T	p.Phe300Phe	synonymous	Exon 9 of 10	NP_071909.1
	SIL1	NM_001037633.2		c.900C>T	p.Phe300Phe	synonymous	Exon 10 of 11	NP_001032722.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIL1	ENST00000394817.7	TSL:1 MANE Select	c.900C>T	p.Phe300Phe	synonymous	Exon 9 of 10	ENSP00000378294.2
	SIL1	ENST00000868003.1		c.1032C>T	p.Phe344Phe	synonymous	Exon 10 of 11	ENSP00000538062.1
	SIL1	ENST00000868009.1		c.1029C>T	p.Phe343Phe	synonymous	Exon 10 of 11	ENSP00000538068.1

Frequencies

GnomAD3 genomes AF: 0.00372 AC: 566 AN: 152258 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.000912 AC: 155 AN: 169984 AF XY: 0.000742

Gnomad AFR exome AF: 0.0142

Gnomad AMR exome AF: 0.000308

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000730

Gnomad OTH exome AF: 0.000216

GnomAD4 exome AF: 0.000339 AC: 478 AN: 1411844 Hom.: 5 Cov.: 32 AF XY: 0.000311 AC XY: 217 AN XY: 697678

African (AFR) AF: 0.0120 AC: 386 AN: 32286

American (AMR) AF: 0.000351 AC: 13 AN: 37072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25262

East Asian (EAS) AF: 0.00 AC: 0 AN: 36922

South Asian (SAS) AF: 0.00 AC: 0 AN: 80280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50022

Middle Eastern (MID) AF: 0.000700 AC: 4 AN: 5714

European-Non Finnish (NFE) AF: 0.0000359 AC: 39 AN: 1085750

Other (OTH) AF: 0.000615 AC: 36 AN: 58536

GnomAD4 genome AF: 0.00372 AC: 567 AN: 152376 Hom.: 3 Cov.: 33 AF XY: 0.00395 AC XY: 294 AN XY: 74510

African (AFR) AF: 0.0128 AC: 534 AN: 41600

American (AMR) AF: 0.00150 AC: 23 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00199 Hom.: 0

Bravo AF: 0.00410

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Marinesco-Sjögren syndrome (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.39
PhyloP100		2.6
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs35080367; hg19: chr5-138286989;