Genetic Variant NM_031464.5:c.532-102C>T (chr14-74911482-G-A) – 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.532-102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,356,996 control chromosomes in the GnomAD database, including 101,146 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 0.30 ( 8714 hom., cov: 31)

Exomes 𝑓: 0.39 ( 92432 hom. )

Consequence

RPS6KL1
NM_031464.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.711

Publications

12 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:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 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
RPS6KL1	NM_031464.5	MANE Select	c.532-102C>T	intron	N/A	NP_113652.2
RPS6KL1	NM_001370252.1		c.532-102C>T	intron	N/A	NP_001357181.1
RPS6KL1	NM_001370253.1		c.487-102C>T	intron	N/A	NP_001357182.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPS6KL1	ENST00000557413.6	TSL:5 MANE Select	c.532-102C>T	intron	N/A	ENSP00000450567.1
RPS6KL1	ENST00000555009.5	TSL:1	n.439-102C>T	intron	N/A	ENSP00000450660.1
RPS6KL1	ENST00000961459.1		c.580-102C>T	intron	N/A	ENSP00000631518.1

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46288

AN:

151916

Hom.:

8714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0808

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.423

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.279

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.376

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.341

GnomAD4 exome

AF:

0.385

AC:

464214

AN:

1204962

Hom.:

92432

Cov.:

AF XY:

0.383

AC XY:

229019

AN XY:

598358

show subpopulations

African (AFR)

AF:

0.0647

AC:

1834

AN:

28332

American (AMR)

AF:

0.481

AC:

17740

AN:

36896

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

8994

AN:

20872

East Asian (EAS)

AF:

0.511

AC:

19295

AN:

37724

South Asian (SAS)

AF:

0.294

AC:

21242

AN:

72176

European-Finnish (FIN)

AF:

0.285

AC:

10048

AN:

35232

Middle Eastern (MID)

AF:

0.383

AC:

1381

AN:

3608

European-Non Finnish (NFE)

AF:

0.396

AC:

363909

AN:

918808

Other (OTH)

AF:

0.385

AC:

19771

AN:

51314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

14359

28718

43077

57436

71795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10930

21860

32790

43720

54650

<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:

0.304

AC:

46291

AN:

152034

Hom.:

8714

Cov.:

AF XY:

0.302

AC XY:

22473

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0805

AC:

3341

AN:

41506

American (AMR)

AF:

0.424

AC:

6482

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

1467

AN:

3472

East Asian (EAS)

AF:

0.552

AC:

2838

AN:

5140

South Asian (SAS)

AF:

0.279

AC:

1347

AN:

4822

European-Finnish (FIN)

AF:

0.266

AC:

2822

AN:

10596

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.396

AC:

26874

AN:

67904

Other (OTH)

AF:

0.341

AC:

718

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1489

2978

4467

5956

7445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.344

Hom.:

1577

Bravo

AF:

0.311

Asia WGS

AF:

0.363

AC:

1263

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.36

(source)

DANN

Benign

0.63

PhyloP100

-0.71

PromoterAI

-0.026

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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