rs4818998

Variant names:

• chr21-44961690-C-T
• rs4818998
• NM_058190.4:c.352+1522C>T

Variant summary

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

The NM_058190.4(SLX9):​c.352+1522C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,080 control chromosomes in the GnomAD database, including 11,821 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 0.39 (11821 hom., cov: 33)
• Consequence: SLX9 NM_058190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.954
• Publications: 3 publications found

Genes affected

SLX9 (HGNC:15811): (SLX9 ribosome biogenesis factor) Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleolus. Predicted to be part of 90S preribosome and preribosome, small subunit precursor. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058190.4. 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
	SLX9	NM_058190.4	MANE Select	c.352+1522C>T		intron	N/A	NP_478070.1	Q9NSI2-1
	SLX9	NM_001316983.2		c.352+1522C>T		intron	N/A	NP_001303912.1
	SLX9	NM_001316984.2		c.307+1522C>T		intron	N/A	NP_001303913.1	Q9NSI2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX9	ENST00000291634.11	TSL:1 MANE Select	c.352+1522C>T		intron	N/A	ENSP00000291634.6	Q9NSI2-1
	SLX9	ENST00000397826.8	TSL:1	c.307+1522C>T		intron	N/A	ENSP00000380926.3	Q9NSI2-2
	SLX9	ENST00000874000.1		c.511+1522C>T		intron	N/A	ENSP00000544059.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58677 AN: 151962 Hom.: 11808 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.386 AC: 58732 AN: 152080 Hom.: 11821 Cov.: 33 AF XY: 0.386 AC XY: 28668 AN XY: 74320

African (AFR) AF: 0.475 AC: 19693 AN: 41480

American (AMR) AF: 0.405 AC: 6187 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1299 AN: 3466

East Asian (EAS) AF: 0.277 AC: 1439 AN: 5186

South Asian (SAS) AF: 0.213 AC: 1025 AN: 4816

European-Finnish (FIN) AF: 0.353 AC: 3723 AN: 10548

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24122 AN: 67984

Other (OTH) AF: 0.358 AC: 756 AN: 2114

Alfa AF: 0.374 Hom.: 1378

Bravo AF: 0.399

Asia WGS AF: 0.262 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.21
DANN	Benign	0.35
PhyloP100		-0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4818998; hg19: chr21-46381605;