5-138947139-C-T

Variant names:

• chr5-138947139-C-T
• NM_022464.5:c.1364G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022464.5(SIL1):​c.1364G>A​(p.Ser455Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SIL1 NM_022464.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10625407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIL1	NM_022464.5	c.1364G>A	p.Ser455Asn	missense_variant	Exon 10 of 10	ENST00000394817.7	NP_071909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIL1	ENST00000394817.7	c.1364G>A	p.Ser455Asn	missense_variant	Exon 10 of 10	1	NM_022464.5	ENSP00000378294.2
SIL1	ENST00000509534.5	c.1385G>A	p.Ser462Asn	missense_variant	Exon 11 of 11	5		ENSP00000426858.1
SIL1	ENST00000265195.9	c.1364G>A	p.Ser455Asn	missense_variant	Exon 11 of 11	5		ENSP00000265195.5
SIL1	ENST00000515008.1	n.699G>A		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Marinesco-Sjögren syndrome Uncertain:1

Nov 06, 2019

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.83	.;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.2	M;M;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.60	N;N;N
REVEL	Benign	0.087
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.015	B;B;B
Vest4		0.078
MutPred		0.17		.;.;Gain of helix (P = 0.0199);
MVP		0.56
MPC		0.23
ClinPred		0.21	T
GERP RS		3.2
Varity_R		0.062
gMVP		0.085

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-138282828;