X-72275603-C-T

Variant names:

• chrX-72275603-C-T
• NM_001007.5:c.203G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001007.5(RPS4X):​c.203G>A​(p.Arg68Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: RPS4X NM_001007.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53
• Publications: 0 publications found

Genes affected

RPS4X (HGNC:10424): (ribosomal protein S4 X-linked) Cytoplasmic ribosomes, organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes ribosomal protein S4, a component of the 40S subunit. Ribosomal protein S4 is the only ribosomal protein known to be encoded by more than one gene, namely this gene and ribosomal protein S4, Y-linked (RPS4Y). The 2 isoforms encoded by these genes are not identical, but are functionally equivalent. Ribosomal protein S4 belongs to the S4E family of ribosomal proteins. This gene is not subject to X-inactivation. It has been suggested that haploinsufficiency of the ribosomal protein S4 genes plays a role in Turner syndrome; however, this hypothesis is controversial. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

PIN4 (HGNC:8992): (peptidylprolyl cis/trans isomerase, NIMA-interacting 4) This gene encodes a member of the parvulin subfamily of the peptidyl-prolyl cis/trans isomerase protein family. The encoded protein catalyzes the isomerization of peptidylprolyl bonds, and may play a role in the cell cycle, chromatin remodeling, and/or ribosome biogenesis. The encoded protein may play an additional role in the mitochondria. [provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS4X	NM_001007.5	MANE Select	c.203G>A	p.Arg68Gln	missense	Exon 3 of 7	NP_000998.1	B2R491

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS4X	ENST00000316084.10	TSL:1 MANE Select	c.203G>A	p.Arg68Gln	missense	Exon 3 of 7	ENSP00000362744.4	P62701
	RPS4X	ENST00000897477.1		c.203G>A	p.Arg68Gln	missense	Exon 3 of 7	ENSP00000567536.1
	RPS4X	ENST00000944636.1		c.203G>A	p.Arg68Gln	missense	Exon 3 of 7	ENSP00000614695.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.49	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.5
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.30
Sift	Benign	0.031	D
Sift4G	Benign	0.14	T
Polyphen		0.17	B
Vest4		0.68
MutPred		0.56		Loss of MoRF binding (P = 0.0284)
MVP		0.87
MPC		1.4
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.67
gMVP		0.87
Mutation Taster		=74/26	polymorphism

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

hg19: chrX-71495453;