NM_014496.5:c.510T>C

Variant names:

• chrX-84135202-A-G
• rs770657822
• NM_014496.5:c.510T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014496.5(RPS6KA6):​c.510T>C​(p.Phe170Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000043 in 1,163,060 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000038 (0 hom. 1 hem.)
• Consequence: RPS6KA6 NM_014496.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA6	NM_014496.5	c.510T>C	p.Phe170Phe	synonymous_variant	Exon 7 of 22	ENST00000262752.5	NP_055311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA6	ENST00000262752.5	c.510T>C	p.Phe170Phe	synonymous_variant	Exon 7 of 22	1	NM_014496.5	ENSP00000262752.2
RPS6KA6	ENST00000620340.4	c.510T>C	p.Phe170Phe	synonymous_variant	Exon 7 of 22	5		ENSP00000483896.1

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111749 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33989

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000956

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000175 AC: 3 AN: 171090 Hom.: 0 AF XY: 0.0000175 AC XY: 1 AN XY: 57080

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000114

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000380 AC: 4 AN: 1051311 Hom.: 0 Cov.: 23 AF XY: 0.00000311 AC XY: 1 AN XY: 321753

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000116

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000895 AC: 1 AN: 111749 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33989

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000956

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	10
DANN	Benign	0.79

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: rs770657822; hg19: chrX-83390210;