X-72275731-C-T

Variant names:

• chrX-72275731-C-T
• rs369740837
• NM_001007.5:c.82-7G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001007.5(RPS4X):​c.82-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000561 in 1,176,974 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000057 (0 hom. 18 hem.)
• Consequence: RPS4X NM_001007.5 splice_region, intron
• Scores: Splicing: ADA: 0.0004291
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.992
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BS2: High Hemizygotes in GnomAdExome4 at 18 gene

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.82-7G>A		splice_region intron	N/A	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.82-7G>A		splice_region intron	N/A	ENSP00000362744.4	P62701
	RPS4X	ENST00000897477.1		c.82-7G>A		splice_region intron	N/A	ENSP00000567536.1
	RPS4X	ENST00000944636.1		c.82-7G>A		splice_region intron	N/A	ENSP00000614695.1

Frequencies

GnomAD3 genomes AF: 0.0000451 AC: 5 AN: 110985 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000290

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000377

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000714 AC: 10 AN: 140049 AF XY: 0.000117

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000221

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000700

Gnomad OTH exome AF: 0.000270

GnomAD4 exome AF: 0.0000572 AC: 61 AN: 1065989 Hom.: 0 Cov.: 30 AF XY: 0.0000528 AC XY: 18 AN XY: 340793

African (AFR) AF: 0.0000785 AC: 2 AN: 25479

American (AMR) AF: 0.000285 AC: 9 AN: 31541

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18898

East Asian (EAS) AF: 0.00 AC: 0 AN: 28797

South Asian (SAS) AF: 0.00 AC: 0 AN: 51116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39059

Middle Eastern (MID) AF: 0.000491 AC: 2 AN: 4072

European-Non Finnish (NFE) AF: 0.0000523 AC: 43 AN: 822122

Other (OTH) AF: 0.000111 AC: 5 AN: 44905

GnomAD4 genome AF: 0.0000451 AC: 5 AN: 110985 Hom.: 0 Cov.: 23 AF XY: 0.0000301 AC XY: 1 AN XY: 33213

African (AFR) AF: 0.00 AC: 0 AN: 30465

American (AMR) AF: 0.000290 AC: 3 AN: 10362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3538

South Asian (SAS) AF: 0.00 AC: 0 AN: 2578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5941

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.0000377 AC: 2 AN: 53063

Other (OTH) AF: 0.00 AC: 0 AN: 1474

Alfa AF: 0.0000364 Hom.: 2

Bravo AF: 0.0000869

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.0
DANN	Benign	0.68
PhyloP100		0.99
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00043
dbscSNV1_RF	Benign	0.046
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

dbSNP: rs369740837; hg19: chrX-71495581;