dbSNP rs3213717: RPS6KL1:c.531+150G>A (chr14-74911644-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_031464.5(RPS6KL1):c.531+150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 749,144 control chromosomes in the GnomAD database, including 9,661 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 0.13 ( 1501 hom., cov: 32)

Exomes 𝑓: 0.15 ( 8160 hom. )

Consequence

RPS6KL1
NM_031464.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0750

Publications

6 publications found

Variant links:

Genes affected

RPS6KL1 (HGNC:20222): (ribosomal protein S6 kinase like 1) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be located in ribosome. [provided by Alliance of Genome Resources, Apr 2022]

RPS6KL1 links:

Genome browser will be placed here

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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031464.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS6KL1	NM_031464.5	MANE Select	c.531+150G>A	intron	N/A	NP_113652.2	Q9Y6S9-1
RPS6KL1	NM_001370252.1		c.531+150G>A	intron	N/A	NP_001357181.1
RPS6KL1	NM_001370253.1		c.486+150G>A	intron	N/A	NP_001357182.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS6KL1	ENST00000557413.6	TSL:5 MANE Select	c.531+150G>A	intron	N/A	ENSP00000450567.1	Q9Y6S9-1
RPS6KL1	ENST00000555009.5	TSL:1	n.438+150G>A	intron	N/A	ENSP00000450660.1	Q9Y6S9-2
RPS6KL1	ENST00000961459.1		c.579+150G>A	intron	N/A	ENSP00000631518.1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19922

AN:

151922

Hom.:

1503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0830

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0839

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.118

GnomAD4 exome

AF:

0.153

AC:

91558

AN:

597102

Hom.:

8160

Cov.:

AF XY:

0.159

AC XY:

49786

AN XY:

312954

show subpopulations

African (AFR)

AF:

0.0793

AC:

1264

AN:

15942

American (AMR)

AF:

0.184

AC:

5297

AN:

28740

Ashkenazi Jewish (ASJ)

AF:

0.0902

AC:

1490

AN:

16522

East Asian (EAS)

AF:

0.195

AC:

6224

AN:

31994

South Asian (SAS)

AF:

0.278

AC:

15008

AN:

53972

European-Finnish (FIN)

AF:

0.192

AC:

8385

AN:

43606

Middle Eastern (MID)

AF:

0.104

AC:

410

AN:

3952

European-Non Finnish (NFE)

AF:

0.132

AC:

49184

AN:

371212

Other (OTH)

AF:

0.138

AC:

4296

AN:

31162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

4156

8313

12469

16626

20782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

822

1644

2466

3288

4110

<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:

0.131

AC:

19919

AN:

152042

Hom.:

1501

Cov.:

AF XY:

0.137

AC XY:

10212

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0828

AC:

3433

AN:

41460

American (AMR)

AF:

0.135

AC:

2066

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0839

AC:

291

AN:

3470

East Asian (EAS)

AF:

0.174

AC:

899

AN:

5176

South Asian (SAS)

AF:

0.288

AC:

1387

AN:

4822

European-Finnish (FIN)

AF:

0.213

AC:

2243

AN:

10548

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9170

AN:

67966

Other (OTH)

AF:

0.115

AC:

244

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

866

1733

2599

3466

4332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.124

Hom.:

151

Bravo

AF:

0.120

Asia WGS

AF:

0.208

AC:

726

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.1

(source)

DANN

Benign

0.46

PhyloP100

0.075

PromoterAI

0.013

Neutral

(source)

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