Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_006013.5(RPL10):c.191C>T(p.Ala64Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 24)

Consequence

RPL10
NM_006013.5 missense, splice_region

Scores

Splicing: ADA: 0.9515

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.29

Publications

6 publications found

Variant links:

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

RPL10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.963

PP5

Variant X-154399803-C-T is Pathogenic according to our data. Variant chrX-154399803-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 430614.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006013.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RPL10	NM_006013.5	MANE Select	c.191C>T	p.Ala64Val	missense splice_region	Exon 5 of 7	NP_006004.3
RPL10	NM_001256577.2		c.191C>T	p.Ala64Val	missense splice_region	Exon 5 of 6	NP_001243506.2
RPL10	NM_001303624.2		c.191C>T	p.Ala64Val	missense splice_region	Exon 4 of 6	NP_001290553.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RPL10	ENST00000369817.7	TSL:5 MANE Select	c.191C>T	p.Ala64Val	missense splice_region	Exon 5 of 7	ENSP00000358832.2
RPL10	ENST00000344746.8	TSL:1	c.191C>T	p.Ala64Val	missense splice_region	Exon 4 of 6	ENSP00000341730.4
RPL10	ENST00000458500.5	TSL:1	c.191C>T	p.Ala64Val	missense splice_region	Exon 5 of 6	ENSP00000395025.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual disability, X-linked, syndromic, 35 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.55

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

0.90

PhyloP100

7.3

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.6

REVEL

Pathogenic

0.83

Sift

Uncertain

0.014

Sift4G

Uncertain

0.0060

Polyphen

0.90

Vest4

0.92

MutPred

0.86

Loss of disorder (P = 0.071)

MVP

0.99

MPC

2.1

ClinPred

0.98

GERP RS

4.9

PromoterAI

-0.040

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.98

Mutation Taster

=44/56

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.95

dbscSNV1_RF

Pathogenic

0.76

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over