chrX-84064396-T-C

Variant names:

• chrX-84064396-T-C
• rs145715341
• NM_014496.5:c.2119A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_014496.5(RPS6KA6):​c.2119A>G​(p.Met707Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000352 in 1,193,229 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 127 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., 9 hem., cov: 22)
  • Exomes 𝑓: 0.00035 (0 hom. 118 hem.)
• Consequence: RPS6KA6 NM_014496.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.46
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008620024).
• BP6: Variant X-84064396-T-C is Benign according to our data. Variant chrX-84064396-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2660996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 9 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.2119A>G	p.Met707Val	missense	Exon 22 of 22	NP_055311.1	Q9UK32-1
	RPS6KA6	NM_001330512.1		c.2119A>G	p.Met707Val	missense	Exon 24 of 24	NP_001317441.1	Q9UK32-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA6	ENST00000262752.5	TSL:1 MANE Select	c.2119A>G	p.Met707Val	missense	Exon 22 of 22	ENSP00000262752.2	Q9UK32-1
	RPS6KA6	ENST00000620340.4	TSL:5	c.2119A>G	p.Met707Val	missense	Exon 22 of 22	ENSP00000483896.1	Q9UK32-2
	RPS6KA6	ENST00000911420.1		c.2080A>G	p.Met694Val	missense	Exon 22 of 22	ENSP00000581479.1

Frequencies

GnomAD3 genomes AF: 0.000385 AC: 42 AN: 109163 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000937

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000228

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000195 AC: 32 AN: 164493 AF XY: 0.0000950

Gnomad AFR exome AF: 0.000963

Gnomad AMR exome AF: 0.000167

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000348 AC: 377 AN: 1084024 Hom.: 0 Cov.: 28 AF XY: 0.000336 AC XY: 118 AN XY: 351504

African (AFR) AF: 0.00104 AC: 27 AN: 25881

American (AMR) AF: 0.000214 AC: 7 AN: 32778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18773

East Asian (EAS) AF: 0.00 AC: 0 AN: 29928

South Asian (SAS) AF: 0.0000593 AC: 3 AN: 50548

European-Finnish (FIN) AF: 0.0000249 AC: 1 AN: 40169

Middle Eastern (MID) AF: 0.000245 AC: 1 AN: 4074

European-Non Finnish (NFE) AF: 0.000386 AC: 323 AN: 836367

Other (OTH) AF: 0.000330 AC: 15 AN: 45506

GnomAD4 genome AF: 0.000394 AC: 43 AN: 109205 Hom.: 0 Cov.: 22 AF XY: 0.000285 AC XY: 9 AN XY: 31549

African (AFR) AF: 0.000969 AC: 29 AN: 29935

American (AMR) AF: 0.000198 AC: 2 AN: 10109

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.00 AC: 0 AN: 3470

South Asian (SAS) AF: 0.00 AC: 0 AN: 2526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 211

European-Non Finnish (NFE) AF: 0.000228 AC: 12 AN: 52624

Other (OTH) AF: 0.00 AC: 0 AN: 1480

Alfa AF: 0.000406 Hom.: 16

Bravo AF: 0.000555

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000692 AC: 2

ESP6500AA AF: 0.000522 AC: 2

ESP6500EA AF: 0.000446 AC: 3

ExAC AF: 0.000214 AC: 26

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	10
DANN	Benign	0.74
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.060	N
PhyloP100		2.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.090
Sift	Benign	0.74	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.024
MVP		0.30
MPC		0.52
ClinPred		0.013	T
GERP RS		3.0
Varity_R		0.24
gMVP		0.32
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs145715341; hg19: chrX-83319404; COSMIC: COSV53119200;