X-47147489-A-G

Variant names:

• chrX-47147489-A-G
• rs1877750604
• NM_005676.5:c.8A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005676.5(RBM10):​c.8A>G​(p.Tyr3Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000273 in 1,098,035 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: RBM10 NM_005676.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3475635).

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.8A>G	p.Tyr3Cys	missense	Exon 2 of 24	NP_005667.2
	RBM10	NM_001204468.2		c.203A>G	p.Tyr68Cys	missense	Exon 2 of 24	NP_001191397.1	P98175-5
	RBM10	NM_001440861.1		c.203A>G	p.Tyr68Cys	missense	Exon 2 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.8A>G	p.Tyr3Cys	missense	Exon 2 of 24	ENSP00000366829.3	P98175-1
	RBM10	ENST00000329236.8	TSL:1	c.203A>G	p.Tyr68Cys	missense	Exon 2 of 24	ENSP00000328848.8	P98175-5
	RBM10	ENST00000628161.2	TSL:1	c.8A>G	p.Tyr3Cys	missense	Exon 2 of 23	ENSP00000486115.1	P98175-4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1098035 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363391

African (AFR) AF: 0.00 AC: 0 AN: 26401

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54142

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40531

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841938

Other (OTH) AF: 0.00 AC: 0 AN: 46090

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.18
Sift	Benign	0.034	D
Sift4G	Benign	0.13	T
Polyphen		0.94	P
Vest4		0.51
MutPred		0.33		Gain of catalytic residue at M1 (P = 2e-04)
MVP		0.70
MPC		1.7
ClinPred		0.86	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.62
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1877750604; hg19: chrX-47006888;