rs915942

chrX-154398397-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_006013.5(RPL10):c.-24+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 886,049 control chromosomes in the GnomAD database, including 6,838 homozygotes. There are 35,176 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (1814 hom., 6157 hem., cov: 25)
  • Exomes 𝑓: 0.13 (5024 hom. 29019 hem.)
• Consequence: RPL10 NM_006013.5 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0003592
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.95

Genes affected

RPL10 (HGNC:10298): (ribosomal protein L10) This gene encodes a ribosomal protein that is a component of the 60S ribosome subunit. The related protein in chicken can bind to c-Jun and can repress c-Jun-mediated transcriptional activation. Some studies have detected an association between variation in this gene and autism spectrum disorders, though others do not detect this relationship. There are multiple pseudogenes of this gene dispersed throughout the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant X-154398397-G-A is Benign according to our data. Variant chrX-154398397-G-A is described in ClinVar as [Benign]. Clinvar id is 1327969.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL10	NM_006013.5	c.-24+3G>A		splice_donor_region_variant, intron_variant		ENST00000369817.7
LOC124905228	XR_007068356.1	n.446C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL10	ENST00000369817.7	c.-24+3G>A		splice_donor_region_variant, intron_variant		5	NM_006013.5	P1
	ENST00000624054.2	n.446C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 20347 AN: 112892 Hom.: 1802 Cov.: 25 AF XY: 0.175 AC XY: 6125 AN XY: 35062

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.00730

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0549

Gnomad EAS AF: 0.0933

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.0625

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.168

GnomAD3 exomes AF: 0.144 AC: 25761 AN: 179374 Hom.: 1588 AF XY: 0.136 AC XY: 8947 AN XY: 65634

Gnomad AFR exome AF: 0.351

Gnomad AMR exome AF: 0.201

Gnomad ASJ exome AF: 0.0559

Gnomad EAS exome AF: 0.0708

Gnomad SAS exome AF: 0.166

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.127 AC: 97883 AN: 773104 Hom.: 5024 Cov.: 13 AF XY: 0.130 AC XY: 29019 AN XY: 223062

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.0600

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.181 AC: 20407 AN: 112945 Hom.: 1814 Cov.: 25 AF XY: 0.175 AC XY: 6157 AN XY: 35125

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.0549

Gnomad4 EAS AF: 0.0925

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.179

Alfa AF: 0.129 Hom.: 2808

Bravo AF: 0.192

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked, syndromic, 35 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	12
Dann	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00036
dbscSNV1_RF	Benign	0.054
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: rs915942; hg19: chrX-153626738; COSMIC: COSV50010006; COSMIC: COSV50010006;