X-84106918-T-G

Variant names:

• chrX-84106918-T-G
• rs143409966
• NM_014496.5:c.1234A>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.1234A>C​(p.Ile412Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: RPS6KA6 NM_014496.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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 (MetaRNN=0.111990124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA6	NM_014496.5	c.1234A>C	p.Ile412Leu	missense_variant	Exon 14 of 22	ENST00000262752.5	NP_055311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA6	ENST00000262752.5	c.1234A>C	p.Ile412Leu	missense_variant	Exon 14 of 22	1	NM_014496.5	ENSP00000262752.2
RPS6KA6	ENST00000620340.4	c.1234A>C	p.Ile412Leu	missense_variant	Exon 14 of 22	5		ENSP00000483896.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 23

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.82
DEOGEN2	Benign	0.088	.;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.66	.;N
REVEL	Benign	0.060
Sift	Benign	0.70	.;T
Sift4G	Benign	1.0	T;T
Polyphen		0.040	.;B
Vest4		0.28
MutPred		0.46		Loss of catalytic residue at V413 (P = 0.0857);Loss of catalytic residue at V413 (P = 0.0857);
MVP		0.68
MPC		0.51
ClinPred		0.31	T
GERP RS		2.6
Varity_R		0.17
gMVP		0.34

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: rs143409966; hg19: chrX-83361926;