rs7580

chrX-72273841-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BA1

The NM_001007.5(RPS4X):c.492G>A(p.Leu164=) 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant X-72273841-C-T is Benign according to our data. Variant chrX-72273841-C-T is described in Lovd as [Benign]. Variant chrX-72273841-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS4X	NM_001007.5	c.492G>A	p.Leu164=	synonymous_variant	5/7	ENST00000316084.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS4X	ENST00000316084.10	c.492G>A	p.Leu164=	synonymous_variant	5/7	1	NM_001007.5	P1
RPS4X	ENST00000486733.2	n.1562G>A		non_coding_transcript_exon_variant	3/5	5
PIN4	ENST00000439980.7	c.238-25141C>T		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.535 AC: 58432 AN: 109172 Hom.: 14477 Cov.: 22 AF XY: 0.524 AC XY: 16503 AN XY: 31494

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

GnomAD3 exomes AF: 0.579 AC: 105265 AN: 181825 Hom.: 22933 AF XY: 0.587 AC XY: 38990 AN XY: 66393

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 SAS exome AF: 0.363

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

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.678

Gnomad4 EAS exome AF: 0.00536

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.747

Gnomad4 NFE exome AF: 0.770

Gnomad4 OTH exome AF: 0.639

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

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.566

Alfa AF: 0.664 Hom.: 8004

Bravo AF: 0.504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	12
Dann	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs7580; hg19: chrX-71493691; COSMIC: COSV60181536; COSMIC: COSV60181536;