X-84134495-T-G

Variant names:

• chrX-84134495-T-G
• rs10218349
• NM_014496.5:c.646+287A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014496.5(RPS6KA6):​c.646+287A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 110,784 control chromosomes in the GnomAD database, including 796 homozygotes. There are 3,987 hemizygotes in GnomAD. 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 0.12 (796 hom., 3987 hem., cov: 23)
• Consequence: RPS6KA6 NM_014496.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA6	NM_014496.5	c.646+287A>C		intron_variant	Intron 8 of 21	ENST00000262752.5	NP_055311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA6	ENST00000262752.5	c.646+287A>C		intron_variant	Intron 8 of 21	1	NM_014496.5	ENSP00000262752.2
RPS6KA6	ENST00000620340.4	c.646+287A>C		intron_variant	Intron 8 of 21	5		ENSP00000483896.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 13462 AN: 110740 Hom.: 797 Cov.: 23 AF XY: 0.121 AC XY: 3989 AN XY: 33010

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.0962

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0644

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.102

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.121 AC: 13455 AN: 110784 Hom.: 796 Cov.: 23 AF XY: 0.121 AC XY: 3987 AN XY: 33064

Gnomad4 AFR AF: 0.0837

Gnomad4 AMR AF: 0.0988

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.102

Alfa AF: 0.109 Hom.: 1939

Bravo AF: 0.119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.82
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs10218349; hg19: chrX-83389503;