X-47169518-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 38 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM10	NM_005676.5	c.201+20C>T		intron_variant		ENST00000377604.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM10	ENST00000377604.8	c.201+20C>T		intron_variant		1	NM_005676.5	A1
RBM10	ENST00000329236.8	c.396+20C>T		intron_variant		1		P3
RBM10	ENST00000628161.2	c.201+20C>T		intron_variant		1
RBM10	ENST00000345781.10	c.201+20C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.000664 AC: 75 AN: 112910 Hom.: 1 Cov.: 23 AF XY: 0.00108 AC XY: 38 AN XY: 35054

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

GnomAD3 exomes AF: 0.00291 AC: 438 AN: 150327 Hom.: 5 AF XY: 0.00490 AC XY: 223 AN XY: 45479

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 SAS exome AF: 0.0262

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

Gnomad4 AFR exome AF: 0.0000383

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000339

Gnomad4 SAS exome AF: 0.0239

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000240

Gnomad4 OTH exome AF: 0.00167

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

Gnomad4 AFR AF: 0.0000641

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0259

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

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

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 11, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.2
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs371753657; hg19: chrX-47028917;