NM_001007.5:c.7C>A

Variant names:

• chrX-72276231-G-T
• rs1179468202
• NM_001007.5:c.7C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001007.5(RPS4X):​c.7C>A​(p.Arg3Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000915 in 1,092,481 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: RPS4X NM_001007.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.89
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.7C>A	p.Arg3Ser	missense	Exon 2 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.7C>A	p.Arg3Ser	missense	Exon 2 of 7	ENSP00000362744.4	P62701
	RPS4X	ENST00000897477.1		c.7C>A	p.Arg3Ser	missense	Exon 2 of 7	ENSP00000567536.1
	RPS4X	ENST00000944636.1		c.7C>A	p.Arg3Ser	missense	Exon 2 of 7	ENSP00000614695.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1092481 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 358033

African (AFR) AF: 0.00 AC: 0 AN: 26261

American (AMR) AF: 0.00 AC: 0 AN: 34937

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19329

East Asian (EAS) AF: 0.00 AC: 0 AN: 30175

South Asian (SAS) AF: 0.00 AC: 0 AN: 53770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40503

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3984

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 837641

Other (OTH) AF: 0.00 AC: 0 AN: 45881

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.67	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		4.9
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.25
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.057	T
Polyphen		0.088	B
Vest4		0.58
MutPred		0.53		Gain of glycosylation at R3 (P = 0.0073)
MVP		0.95
MPC		1.7
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.98
gMVP		0.72
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1179468202; hg19: chrX-71496081;