rs4818998

Positions:

• chr21-44961690-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX9	NM_058190.4	c.352+1522C>T		intron_variant		ENST00000291634.11	NP_478070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX9	ENST00000291634.11	c.352+1522C>T		intron_variant		1	NM_058190.4	ENSP00000291634
SLX9	ENST00000397826.8	c.307+1522C>T		intron_variant		1		ENSP00000380926	P1
SLX9	ENST00000458015.1	c.307+1522C>T		intron_variant		5		ENSP00000404964
SLX9	ENST00000479127.5	n.248+1522C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.358

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.21
DANN	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs4818998; hg19: chr21-46381605;