dbSNP rs779321218: RPS6KA6:p.Val87Val (chrX-84148121-A-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014496.5(RPS6KA6):c.261T>G(p.Val87Val) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000474 in 1,032,668 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000047 ( 0 hom. 15 hem. )

Consequence

RPS6KA6
NM_014496.5 splice_region, synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.345

Publications

0 publications found

Variant links:

Genes affected

RPS6KA6 (HGNC:10435): (ribosomal protein S6 kinase A6) This gene encodes a member of ribosomal S6 kinase family, serine-threonine protein kinases which are regulated by growth factors. The encoded protein may be distinct from other members of this family, however, as studies suggest it is not growth factor dependent and may not participate in the same signaling pathways. [provided by RefSeq, Jan 2010]

RPS6KA6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant X-84148121-A-C is Benign according to our data. Variant chrX-84148121-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2660997.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.345 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 15 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014496.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA6	NM_014496.5	MANE Select	c.261T>G	p.Val87Val	splice_region synonymous	Exon 4 of 22	NP_055311.1	Q9UK32-1
	RPS6KA6	NM_001330512.1		c.261T>G	p.Val87Val	splice_region synonymous	Exon 6 of 24	NP_001317441.1	Q9UK32-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS6KA6	ENST00000262752.5	TSL:1 MANE Select	c.261T>G	p.Val87Val	splice_region synonymous	Exon 4 of 22	ENSP00000262752.2	Q9UK32-1
RPS6KA6	ENST00000620340.4	TSL:5	c.261T>G	p.Val87Val	splice_region synonymous	Exon 4 of 22	ENSP00000483896.1	Q9UK32-2
RPS6KA6	ENST00000911420.1		c.261T>G	p.Val87Val	splice_region synonymous	Exon 4 of 22	ENSP00000581479.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000254

AC:

AN:

157408

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000544

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000474

AC:

AN:

1032668

Hom.:

Cov.:

AF XY:

0.0000483

AC XY:

AN XY:

310822

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24083

American (AMR)

AF:

0.00

AC:

AN:

29767

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18205

East Asian (EAS)

AF:

0.00

AC:

AN:

29654

South Asian (SAS)

AF:

0.00

AC:

AN:

48222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3859

European-Non Finnish (NFE)

AF:

0.0000616

AC:

AN:

795590

Other (OTH)

AF:

0.00

AC:

AN:

43438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

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

Cov.:

Alfa

AF:

0.0000510

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

7.7

(source)

DANN

Benign

0.87

PhyloP100

0.34

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over