chr5-139283108-T-G

Variant names:

• chr5-139283108-T-G
• rs877826
• ENST00000505522.6:n.592T>G

Variant summary

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

The ENST00000505522.6(SNHG4):​n.592T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,226 control chromosomes in the GnomAD database, including 23,161 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 0.50 (23154 hom., cov: 33)
  • Exomes 𝑓: 0.66 (7 hom.)
• Consequence: SNHG4 ENST00000505522.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498
• Publications: 5 publications found

Genes affected

SNHG4 (HGNC:32964): (small nucleolar RNA host gene 4)

MATR3 (HGNC:6912): (matrin 3) This gene encodes a nuclear matrix protein, which is proposed to stabilize certain messenger RNA species. Mutations of this gene are associated with distal myopathy 2, which often includes vocal cord and pharyngeal weakness. Alternatively spliced transcript variants, including read-through transcripts composed of the upstream small nucleolar RNA host gene 4 (non-protein coding) and matrin 3 gene sequence, have been identified. Pseudogenes of this gene are located on chromosomes 1 and X. [provided by RefSeq, Aug 2013]

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)

LOC124901081 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000505522.6. 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
	SNHG4	NR_036536.2		n.622T>G		non_coding_transcript_exon	Exon 5 of 5
	SNHG4	NR_182751.1		n.746T>G		non_coding_transcript_exon	Exon 6 of 6
	SNHG4	NR_182752.1		n.812T>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNHG4	ENST00000505522.6	TSL:1	n.592T>G		non_coding_transcript_exon	Exon 5 of 5
	MATR3	ENST00000502929.5	TSL:2	c.-404+3979T>G		intron	N/A	ENSP00000422319.1
	SNHG4	ENST00000507197.5	TSL:2	n.729T>G		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76085 AN: 152070 Hom.: 23160 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.658 AC: 25 AN: 38 Hom.: 7 Cov.: 0 AF XY: 0.615 AC XY: 16 AN XY: 26

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.719 AC: 23 AN: 32

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.500 AC: 76082 AN: 152188 Hom.: 23154 Cov.: 33 AF XY: 0.496 AC XY: 36892 AN XY: 74388

African (AFR) AF: 0.158 AC: 6585 AN: 41548

American (AMR) AF: 0.557 AC: 8511 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2122 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1022 AN: 5178

South Asian (SAS) AF: 0.611 AC: 2952 AN: 4828

European-Finnish (FIN) AF: 0.618 AC: 6545 AN: 10584

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46513 AN: 67976

Other (OTH) AF: 0.532 AC: 1124 AN: 2112

Alfa AF: 0.606 Hom.: 6643

Bravo AF: 0.478

Asia WGS AF: 0.380 AC: 1324 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	1.5
DANN	Benign	0.50
PhyloP100		-0.50
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: rs877826; hg19: chr5-138618797;