chr5-138955716-A-G

Variant names:

• chr5-138955716-A-G
• rs7717375
• NM_022464.5:c.768-3832T>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.768-3832T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,094 control chromosomes in the GnomAD database, including 14,139 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 (14139 hom., cov: 33)
• Consequence: SIL1 NM_022464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 4 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)

LOC124901079 (HGNC:):

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 (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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIL1	NM_022464.5	MANE Select	c.768-3832T>C		intron	N/A	NP_071909.1
	SIL1	NM_001037633.2		c.768-3832T>C		intron	N/A	NP_001032722.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIL1	ENST00000394817.7	TSL:1 MANE Select	c.768-3832T>C		intron	N/A	ENSP00000378294.2
	SIL1	ENST00000505945.1	TSL:1	c.186-3832T>C		intron	N/A	ENSP00000425136.1
	SIL1	ENST00000509534.5	TSL:5	c.789-3832T>C		intron	N/A	ENSP00000426858.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63267 AN: 151976 Hom.: 14105 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.416 AC: 63342 AN: 152094 Hom.: 14139 Cov.: 33 AF XY: 0.413 AC XY: 30662 AN XY: 74330

African (AFR) AF: 0.599 AC: 24817 AN: 41456

American (AMR) AF: 0.336 AC: 5137 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1460 AN: 3470

East Asian (EAS) AF: 0.135 AC: 698 AN: 5180

South Asian (SAS) AF: 0.334 AC: 1612 AN: 4820

European-Finnish (FIN) AF: 0.375 AC: 3966 AN: 10564

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24449 AN: 67988

Other (OTH) AF: 0.377 AC: 797 AN: 2114

Alfa AF: 0.384 Hom.: 8739

Bravo AF: 0.420

Asia WGS AF: 0.246 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.32
PhyloP100		-0.087
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: rs7717375; hg19: chr5-138291405;