chrX-47169486-G-T

Position:

• chrX-47169486-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_005676.5(RBM10):​c.189G>T​(p.Glu63Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: RBM10 NM_005676.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.273

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), RBM10. . Gene score misZ 4.4623 (greater than the threshold 3.09). GenCC has associacion of gene with TARP syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.1149348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM10	NM_005676.5	c.189G>T	p.Glu63Asp	missense_variant	3/24	ENST00000377604.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM10	ENST00000377604.8	c.189G>T	p.Glu63Asp	missense_variant	3/24	1	NM_005676.5	A1
RBM10	ENST00000329236.8	c.384G>T	p.Glu128Asp	missense_variant	3/24	1		P3
RBM10	ENST00000628161.2	c.189G>T	p.Glu63Asp	missense_variant	3/23	1
RBM10	ENST00000345781.10	c.189G>T	p.Glu63Asp	missense_variant	3/23	2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.189G>T (p.E63D) alteration is located in exon 3 (coding exon 2) of the RBM10 gene. This alteration results from a G to T substitution at nucleotide position 189, causing the glutamic acid (E) at amino acid position 63 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.;.;.
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L;.
MutationTaster	Benign	0.95	N;N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.72	N;.;N;.
REVEL	Benign	0.024
Sift	Pathogenic	0.0	D;.;T;.
Sift4G	Benign	0.48	T;T;T;T
Polyphen		0.98	D;P;P;.
Vest4		0.17
MutPred		0.17		Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);.;
MVP		0.54
MPC		2.0
ClinPred		0.72	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Varity_R		0.37
gMVP		0.42

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-47028885; COSMIC: COSV61307939;