Variant rs7580 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.97

Variant links:

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]

RPS4X links:

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]

PIN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
RPS4X	NM_001007.5 linkuse as main transcript	c.492G>A	p.Leu164=	synonymous_variant	5/7	ENST00000316084.10	NP_000998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RPS4X	ENST00000316084.10 linkuse as main transcript	c.492G>A	p.Leu164=	synonymous_variant	5/7	1	NM_001007.5	ENSP00000362744	P1
RPS4X	ENST00000486733.2 linkuse as main transcript	n.1562G>A		non_coding_transcript_exon_variant	3/5	5
PIN4	ENST00000439980.7 linkuse as main transcript	c.238-25141C>T		intron_variant, NMD_transcript_variant		4		ENSP00000394066

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

58432

AN:

109172

Hom.:

14477

Cov.:

AF XY:

0.524

AC XY:

16503

AN XY:

31494

show subpopulations

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

show subpopulations

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.:

AF XY:

0.689

AC XY:

249391

AN XY:

361947

show subpopulations

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.:

AF XY:

0.523

AC XY:

16512

AN XY:

31559

show subpopulations

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over