X-72273841-C-T

Variant names:

• chrX-72273841-C-T
• rs7580
• NM_001007.5:c.492G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001007.5(RPS4X):​c.492G>A​(p.Leu164Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.535 in 109,227 control chromosomes in the GnomAD database, including 14,472 homozygotes. There are 16,512 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 0.53 (14472 hom., 16512 hem., cov: 22)
  • Exomes 𝑓: 0.70 (193242 hom. 249391 hem.)
  • Failed GnomAD Quality Control
• Consequence: RPS4X NM_001007.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.97
• Publications: 19 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS4X	NM_001007.5	MANE Select	c.492G>A	p.Leu164Leu	synonymous	Exon 5 of 7	NP_000998.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS4X	ENST00000316084.10	TSL:1 MANE Select	c.492G>A	p.Leu164Leu	synonymous	Exon 5 of 7	ENSP00000362744.4
	RPS4X	ENST00000486733.2	TSL:5	n.1562G>A		non_coding_transcript_exon	Exon 3 of 5
	PIN4	ENST00000439980.7	TSL:4	n.238-25141C>T		intron	N/A	ENSP00000394066.3

Frequencies

GnomAD3 genomes AF: 0.535 AC: 58432 AN: 109172 Hom.: 14477 Cov.: 22

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.0142

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.568

GnomAD2 exomes AF: 0.579 AC: 105265 AN: 181825 AF XY: 0.587

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.525

Gnomad ASJ exome AF: 0.673

Gnomad EAS exome AF: 0.00882

Gnomad FIN exome AF: 0.745

Gnomad NFE exome AF: 0.770

Gnomad OTH exome AF: 0.658

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.699 AC: 765705 AN: 1096211 Hom.: 193242 Cov.: 31 AF XY: 0.689 AC XY: 249391 AN XY: 361947

African (AFR) AF: 0.138 AC: 3652 AN: 26374

American (AMR) AF: 0.534 AC: 18703 AN: 35041

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 13127 AN: 19371

East Asian (EAS) AF: 0.00536 AC: 162 AN: 30198

South Asian (SAS) AF: 0.375 AC: 20245 AN: 54057

European-Finnish (FIN) AF: 0.747 AC: 30221 AN: 40482

Middle Eastern (MID) AF: 0.700 AC: 2891 AN: 4132

European-Non Finnish (NFE) AF: 0.770 AC: 647283 AN: 840546

Other (OTH) AF: 0.639 AC: 29421 AN: 46010

GnomAD4 genome AF: 0.535 AC: 58432 AN: 109227 Hom.: 14472 Cov.: 22 AF XY: 0.523 AC XY: 16512 AN XY: 31559

African (AFR) AF: 0.150 AC: 4529 AN: 30179

American (AMR) AF: 0.541 AC: 5472 AN: 10118

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 1760 AN: 2626

East Asian (EAS) AF: 0.0143 AC: 50 AN: 3507

South Asian (SAS) AF: 0.333 AC: 837 AN: 2513

European-Finnish (FIN) AF: 0.752 AC: 4187 AN: 5569

Middle Eastern (MID) AF: 0.646 AC: 137 AN: 212

European-Non Finnish (NFE) AF: 0.767 AC: 40156 AN: 52339

Other (OTH) AF: 0.566 AC: 846 AN: 1495

Alfa AF: 0.664 Hom.: 8004

Bravo AF: 0.504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs7580; hg19: chrX-71493691; COSMIC: COSV60181536; COSMIC: COSV60181536;