X-84134495-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA6	NM_014496.5	MANE Select	c.646+287A>C		intron	N/A	NP_055311.1
	RPS6KA6	NM_001330512.1		c.646+287A>C		intron	N/A	NP_001317441.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA6	ENST00000262752.5	TSL:1 MANE Select	c.646+287A>C		intron	N/A	ENSP00000262752.2
	RPS6KA6	ENST00000620340.4	TSL:5	c.646+287A>C		intron	N/A	ENSP00000483896.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 13462 AN: 110740 Hom.: 797 Cov.: 23

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

African (AFR) AF: 0.0837 AC: 2570 AN: 30705

American (AMR) AF: 0.0988 AC: 1027 AN: 10390

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 350 AN: 2630

East Asian (EAS) AF: 0.514 AC: 1770 AN: 3445

South Asian (SAS) AF: 0.263 AC: 695 AN: 2638

European-Finnish (FIN) AF: 0.142 AC: 831 AN: 5869

Middle Eastern (MID) AF: 0.0708 AC: 15 AN: 212

European-Non Finnish (NFE) AF: 0.113 AC: 5977 AN: 52704

Other (OTH) AF: 0.102 AC: 154 AN: 1505

Alfa AF: 0.108 Hom.: 2251

Bravo AF: 0.119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.82
DANN	Benign	0.60
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10218349; hg19: chrX-83389503;