chr21-44958579-G-A

Position:

• chr21-44958579-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_058190.4(SLX9):​c.284-1521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,190 control chromosomes in the GnomAD database, including 14,640 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 0.40 (14640 hom., cov: 34)
• Consequence: SLX9 NM_058190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX9	NM_058190.4	c.284-1521G>A		intron_variant		ENST00000291634.11	NP_478070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX9	ENST00000291634.11	c.284-1521G>A		intron_variant		1	NM_058190.4	ENSP00000291634
SLX9	ENST00000397826.8	c.239-1521G>A		intron_variant		1		ENSP00000380926	P1
SLX9	ENST00000458015.1	c.239-1521G>A		intron_variant		5		ENSP00000404964
SLX9	ENST00000479127.5	n.179+155G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60785 AN: 152072 Hom.: 14638 Cov.: 34

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.399 AC: 60789 AN: 152190 Hom.: 14640 Cov.: 34 AF XY: 0.408 AC XY: 30379 AN XY: 74402

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.431

Alfa AF: 0.442 Hom.: 2067

Bravo AF: 0.375

Asia WGS AF: 0.587 AC: 2038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.50

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: rs881317; hg19: chr21-46378494;