X-84164344-T-A

Position:

• chrX-84164344-T-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_014496.5(RPS6KA6):​c.125A>T​(p.Glu42Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000148 in 1,079,508 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000015 (0 hom. 6 hem.)
• Consequence: RPS6KA6 NM_014496.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2084873).
• BS2: High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA6	NM_014496.5	c.125A>T	p.Glu42Val	missense_variant	2/22	ENST00000262752.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA6	ENST00000262752.5	c.125A>T	p.Glu42Val	missense_variant	2/22	1	NM_014496.5	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.0000114 AC: 2 AN: 175753 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 60705

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000251

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000148 AC: 16 AN: 1079508 Hom.: 0 Cov.: 26 AF XY: 0.0000173 AC XY: 6 AN XY: 347166

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000193

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Benign	0.95
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.52	T
Sift4G	Benign	0.11	T;T
Polyphen		0.049	.;B
Vest4		0.27
MutPred		0.32		Gain of catalytic residue at E42 (P = 0.0286);Gain of catalytic residue at E42 (P = 0.0286);
MVP		0.80
MPC		0.60
ClinPred		0.30	T
GERP RS		3.1
Varity_R		0.23
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs1305128818; hg19: chrX-83419352;