X-47169344-A-G

Position:

• chrX-47169344-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_005676.5(RBM10):​c.47A>G​(p.Tyr16Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RBM10 NM_005676.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02

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 2 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=0.36431187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM10	NM_005676.5	c.47A>G	p.Tyr16Cys	missense_variant	3/24	ENST00000377604.8	NP_005667.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM10	ENST00000377604.8	c.47A>G	p.Tyr16Cys	missense_variant	3/24	1	NM_005676.5	ENSP00000366829	A1
RBM10	ENST00000329236.8	c.242A>G	p.Tyr81Cys	missense_variant	3/24	1		ENSP00000328848	P3
RBM10	ENST00000628161.2	c.47A>G	p.Tyr16Cys	missense_variant	3/23	1		ENSP00000486115
RBM10	ENST00000345781.10	c.47A>G	p.Tyr16Cys	missense_variant	3/23	2		ENSP00000329659

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Apr 27, 2021

Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;.;.;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M;M;.
MutationTaster	Benign	0.98	D;N;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-4.5	D;.;D;.
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;.;T;.
Sift4G	Uncertain	0.017	D;T;T;D
Polyphen		1.0	D;D;D;.
Vest4		0.51
MutPred		0.39		Loss of phosphorylation at Y16 (P = 0.0241);Loss of phosphorylation at Y16 (P = 0.0241);Loss of phosphorylation at Y16 (P = 0.0241);.;
MVP		0.75
MPC		1.7
ClinPred		1.0	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.74
gMVP		0.79

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-47028743; COSMIC: COSV61310702;