X-47169518-C-T

Variant names:

• chrX-47169518-C-T
• rs371753657
• NM_005676.5:c.201+20C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005676.5(RBM10):​c.201+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,193,164 control chromosomes in the GnomAD database, including 13 homozygotes. There are 755 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00066 (1 hom., 37 hem., cov: 23)
  • Exomes 𝑓: 0.0012 (12 hom. 718 hem.)
• Consequence: RBM10 NM_005676.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0480
• Publications: 1 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: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-47169518-C-T is Benign according to our data. Variant chrX-47169518-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000655 (74/112963) while in subpopulation SAS AF = 0.0259 (71/2742). AF 95% confidence interval is 0.0211. There are 1 homozygotes in GnomAd4. There are 37 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 37 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM10	NM_005676.5	c.201+20C>T		intron_variant	Intron 3 of 23	ENST00000377604.8	NP_005667.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM10	ENST00000377604.8	c.201+20C>T		intron_variant	Intron 3 of 23	1	NM_005676.5	ENSP00000366829.3
RBM10	ENST00000329236.8	c.396+20C>T		intron_variant	Intron 3 of 23	1		ENSP00000328848.8
RBM10	ENST00000628161.2	c.201+20C>T		intron_variant	Intron 3 of 22	1		ENSP00000486115.1
RBM10	ENST00000345781.10	c.201+20C>T		intron_variant	Intron 3 of 22	2		ENSP00000329659.6

Frequencies

GnomAD3 genomes AF: 0.000664 AC: 75 AN: 112910 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.0000642

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0262

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00291 AC: 438 AN: 150327 AF XY: 0.00490

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000255

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00125 AC: 1349 AN: 1080201 Hom.: 12 Cov.: 30 AF XY: 0.00205 AC XY: 718 AN XY: 350163

African (AFR) AF: 0.0000383 AC: 1 AN: 26087

American (AMR) AF: 0.00 AC: 0 AN: 32845

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19073

East Asian (EAS) AF: 0.0000339 AC: 1 AN: 29510

South Asian (SAS) AF: 0.0239 AC: 1248 AN: 52170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38865

Middle Eastern (MID) AF: 0.000949 AC: 3 AN: 3161

European-Non Finnish (NFE) AF: 0.0000240 AC: 20 AN: 833102

Other (OTH) AF: 0.00167 AC: 76 AN: 45388

GnomAD4 genome AF: 0.000655 AC: 74 AN: 112963 Hom.: 1 Cov.: 23 AF XY: 0.00105 AC XY: 37 AN XY: 35117

African (AFR) AF: 0.0000641 AC: 2 AN: 31205

American (AMR) AF: 0.00 AC: 0 AN: 10812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3541

South Asian (SAS) AF: 0.0259 AC: 71 AN: 2742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53269

Other (OTH) AF: 0.00 AC: 0 AN: 1558

Alfa AF: 0.000217 Hom.: 2

Bravo AF: 0.000155

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 11, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.55
PhyloP100		-0.048
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs371753657; hg19: chrX-47028917;