rs915942

Variant names:

• chrX-154398397-G-A
• rs915942
• ENST00000482732.1:n.10G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000482732.1(RPL10):​n.10G>A variant causes a non coding transcript exon 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 ENST00000482732.1 non_coding_transcript_exon
• Scores: Splicing: ADA: 0.0003592
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.95
• Publications: 15 publications found

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]

RPL10 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked, syndromic, 35

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: MODERATE Submitted by: ClinGen
• X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• autism, susceptibility to, X-linked 5

  Inheritance: Unknown, XL Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000280195 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 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 VariationId is 1327969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
RPL10	NM_006013.5	c.-24+3G>A		splice_region_variant, intron_variant	Intron 1 of 6	ENST00000369817.7	NP_006004.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL10	ENST00000369817.7	c.-24+3G>A		splice_region_variant, intron_variant	Intron 1 of 6	5	NM_006013.5	ENSP00000358832.2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 20347 AN: 112892 Hom.: 1802 Cov.: 25

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

GnomAD2 exomes AF: 0.144 AC: 25761 AN: 179374 AF XY: 0.136

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 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

African (AFR) AF: 0.343 AC: 6842 AN: 19972

American (AMR) AF: 0.197 AC: 6832 AN: 34727

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 1043 AN: 17371

East Asian (EAS) AF: 0.107 AC: 3078 AN: 28706

South Asian (SAS) AF: 0.171 AC: 8158 AN: 47682

European-Finnish (FIN) AF: 0.148 AC: 5283 AN: 35646

Middle Eastern (MID) AF: 0.0687 AC: 245 AN: 3564

European-Non Finnish (NFE) AF: 0.112 AC: 61673 AN: 550127

Other (OTH) AF: 0.134 AC: 4729 AN: 35309

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

African (AFR) AF: 0.341 AC: 10606 AN: 31071

American (AMR) AF: 0.172 AC: 1867 AN: 10832

Ashkenazi Jewish (ASJ) AF: 0.0549 AC: 146 AN: 2661

East Asian (EAS) AF: 0.0925 AC: 331 AN: 3579

South Asian (SAS) AF: 0.164 AC: 458 AN: 2801

European-Finnish (FIN) AF: 0.143 AC: 899 AN: 6280

Middle Eastern (MID) AF: 0.0685 AC: 15 AN: 219

European-Non Finnish (NFE) AF: 0.109 AC: 5803 AN: 53267

Other (OTH) AF: 0.179 AC: 277 AN: 1550

Alfa AF: 0.142 Hom.: 4540

Bravo AF: 0.192

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Nov 07, 2021

Genome-Nilou Lab

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	-0.28
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		2.9
PromoterAI		-0.11	Neutral
Mutation Taster		=79/21	polymorphism (auto)

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

Other links and lift over

dbSNP: rs915942; hg19: chrX-153626738; COSMIC: COSV50010006; COSMIC: COSV50010006;