Genetic Variant SLX9:c.284-1568G>C (chr21-44958532-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_058190.4(SLX9):c.284-1568G>C 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 152,276 control chromosomes in the GnomAD database, including 14,629 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 ( 14615 hom., cov: 33)

Exomes 𝑓: 0.52 ( 14 hom. )

Consequence

SLX9
NM_058190.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.138

Publications

1 publications found

Variant links:

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]

SLX9 links:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.628 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLX9	NM_058190.4	MANE Select	c.284-1568G>C	intron	N/A	NP_478070.1	Q9NSI2-1
SLX9	NM_001316983.2		c.284-1568G>C	intron	N/A	NP_001303912.1
SLX9	NM_001316984.2		c.239-1568G>C	intron	N/A	NP_001303913.1	Q9NSI2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLX9	ENST00000291634.11	TSL:1 MANE Select	c.284-1568G>C	intron	N/A	ENSP00000291634.6	Q9NSI2-1
SLX9	ENST00000397826.8	TSL:1	c.239-1568G>C	intron	N/A	ENSP00000380926.3	Q9NSI2-2
SLX9	ENST00000874000.1		c.284-243G>C	intron	N/A	ENSP00000544059.1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60745

AN:

152066

Hom.:

14613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.646

Gnomad FIN

AF:

0.541

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.496

Gnomad OTH

AF:

0.428

GnomAD4 exome

AF:

0.522

AC:

AN:

Hom.:

AF XY:

0.471

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.474

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.399

AC:

60750

AN:

152184

Hom.:

14615

Cov.:

AF XY:

0.408

AC XY:

30347

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.123

AC:

5106

AN:

41536

American (AMR)

AF:

0.448

AC:

6857

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1555

AN:

3472

East Asian (EAS)

AF:

0.621

AC:

3211

AN:

5168

South Asian (SAS)

AF:

0.646

AC:

3116

AN:

4820

European-Finnish (FIN)

AF:

0.541

AC:

5733

AN:

10604

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.496

AC:

33701

AN:

67966

Other (OTH)

AF:

0.431

AC:

911

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1712

3424

5136

6848

8560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<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:

0.312

Hom.:

975

Bravo

AF:

0.375

Asia WGS

AF:

0.587

AC:

2041

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

1.7

(source)

DANN

Benign

0.44

PhyloP100

0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over