21-44961649-T-A

Variant names:

• chr21-44961649-T-A
• rs9981033
• NM_058190.4:c.352+1481T>A

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+1481T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,230 control chromosomes in the GnomAD database, including 2,390 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 0.17 (2390 hom., cov: 33)
• Consequence: SLX9 NM_058190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX9	NM_058190.4	MANE Select	c.352+1481T>A		intron	N/A	NP_478070.1
	SLX9	NM_001316983.2		c.352+1481T>A		intron	N/A	NP_001303912.1
	SLX9	NM_001316984.2		c.307+1481T>A		intron	N/A	NP_001303913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX9	ENST00000291634.11	TSL:1 MANE Select	c.352+1481T>A		intron	N/A	ENSP00000291634.6
	SLX9	ENST00000397826.8	TSL:1	c.307+1481T>A		intron	N/A	ENSP00000380926.3
	SLX9	ENST00000458015.1	TSL:5	c.307+1481T>A		intron	N/A	ENSP00000404964.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26231 AN: 152112 Hom.: 2391 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.172 AC: 26249 AN: 152230 Hom.: 2390 Cov.: 33 AF XY: 0.174 AC XY: 12914 AN XY: 74426

African (AFR) AF: 0.124 AC: 5154 AN: 41538

American (AMR) AF: 0.167 AC: 2550 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3472

East Asian (EAS) AF: 0.167 AC: 868 AN: 5186

South Asian (SAS) AF: 0.156 AC: 753 AN: 4826

European-Finnish (FIN) AF: 0.197 AC: 2089 AN: 10600

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13607 AN: 67996

Other (OTH) AF: 0.172 AC: 363 AN: 2116

Alfa AF: 0.178 Hom.: 315

Bravo AF: 0.171

Asia WGS AF: 0.153 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.55
PhyloP100		0.040
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: rs9981033; hg19: chr21-46381564;