X-47180249-A-T

Variant names:

• chrX-47180249-A-T
• rs1556778373
• NM_005676.5:c.1100A>T

Variant summary

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

The NM_005676.5(RBM10):​c.1100A>T​(p.His367Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H367P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: RBM10 NM_005676.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.08
• 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=0.28961635).

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.1100A>T	p.His367Leu	missense	Exon 11 of 24	NP_005667.2
	RBM10	NM_001204468.2		c.1295A>T	p.His432Leu	missense	Exon 11 of 24	NP_001191397.1	P98175-5
	RBM10	NM_001440861.1		c.1292A>T	p.His431Leu	missense	Exon 11 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.1100A>T	p.His367Leu	missense	Exon 11 of 24	ENSP00000366829.3	P98175-1
	RBM10	ENST00000329236.8	TSL:1	c.1295A>T	p.His432Leu	missense	Exon 11 of 24	ENSP00000328848.8	P98175-5
	RBM10	ENST00000628161.2	TSL:1	c.866A>T	p.His289Leu	missense	Exon 10 of 23	ENSP00000486115.1	P98175-4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Uncertain	0.61	D
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.071
Sift	Uncertain	0.011	D
Sift4G	Benign	0.15	T
Polyphen		0.97	D
Vest4		0.33
MutPred		0.51		Gain of catalytic residue at H367 (P = 0.0045)
MVP		0.61
MPC		1.7
ClinPred		0.87	D
GERP RS		3.4
Varity_R		0.43
gMVP		0.94
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1556778373; hg19: chrX-47039648;