rs1934470534

Variant names:

• chrX-47169411-CATGGACTACCGTTCAT-C
• rs1934470534
• NM_005676.5:c.117_132delGGACTACCGTTCATAT

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_005676.5(RBM10):​c.117_132delGGACTACCGTTCATAT​(p.Met39IlefsTer90) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 23)
• Consequence: RBM10 NM_005676.5 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.98
• Publications: 0 publications found

Genes affected

RBM10 (HGNC:9896): (RNA binding motif protein 10) This gene encodes a nuclear protein that belongs to a family proteins that contain an RNA-binding motif. The encoded protein associates with hnRNP proteins and may be involved in regulating alternative splicing. Defects in this gene are the cause of the X-linked recessive disorder, TARP syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2011]

RBM10 Gene-Disease associations (from GenCC):

• TARP syndrome

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant X-47169411-CATGGACTACCGTTCAT-C is Pathogenic according to our data. Variant chrX-47169411-CATGGACTACCGTTCAT-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 986344.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005676.5. 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
	RBM10	NM_005676.5	MANE Select	c.117_132delGGACTACCGTTCATAT	p.Met39IlefsTer90	frameshift	Exon 3 of 24	NP_005667.2
	RBM10	NM_001204468.2		c.312_327delGGACTACCGTTCATAT	p.Met104IlefsTer90	frameshift	Exon 3 of 24	NP_001191397.1	P98175-5
	RBM10	NM_001440861.1		c.312_327delGGACTACCGTTCATAT	p.Met104IlefsTer90	frameshift	Exon 3 of 24	NP_001427790.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM10	ENST00000377604.8	TSL:1 MANE Select	c.117_132delGGACTACCGTTCATAT	p.Met39IlefsTer90	frameshift	Exon 3 of 24	ENSP00000366829.3	P98175-1
	RBM10	ENST00000329236.8	TSL:1	c.312_327delGGACTACCGTTCATAT	p.Met104IlefsTer90	frameshift	Exon 3 of 24	ENSP00000328848.8	P98175-5
	RBM10	ENST00000628161.2	TSL:1	c.117_132delGGACTACCGTTCATAT	p.Met39IlefsTer41	frameshift	Exon 3 of 23	ENSP00000486115.1	P98175-4

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	TARP syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1934470534; hg19: chrX-47028810;