dbSNP rs877826: SNHG4:n.592T>G (chr5-139283108-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.498

Publications

5 publications found

Variant links:

Genes affected

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

SNHG4 links:

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]

MATR3 links:

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)

SIL1 links:

LOC124901081 (HGNC:):

LOC124901081 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
SNHG4	NR_036536.2 link	n.622T>G	non_coding_transcript_exon_variant	Exon 5 of 5
SNHG4	NR_182751.1 link	n.746T>G	non_coding_transcript_exon_variant	Exon 6 of 6
SNHG4	NR_182752.1 link	n.812T>G	non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATR3	ENST00000502929.5 link	c.-404+3979T>G		intron_variant	Intron 4 of 19	2		ENSP00000422319.1		A8MXP9

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

76085

AN:

152070

Hom.:

23160

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.615

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.719

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.500

AC:

76082

AN:

152188

Hom.:

23154

Cov.:

AF XY:

0.496

AC XY:

36892

AN XY:

74388

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1587

3175

4762

6350

7937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.5

(source)

DANN

Benign

0.50

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over