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GeneBe

X-154399803-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 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

8
5
1
Splicing: ADA: 0.9515
1
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.29
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 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 id is 430614.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-154399803-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL10NM_006013.5 linkuse as main transcriptc.191C>T p.Ala64Val missense_variant, splice_region_variant 5/7 ENST00000369817.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL10ENST00000369817.7 linkuse as main transcriptc.191C>T p.Ala64Val missense_variant, splice_region_variant 5/75 NM_006013.5 P1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
24

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Intellectual disability, X-linked, syndromic, 35 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.38
Cadd
Pathogenic
33
Dann
Uncertain
1.0
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Pathogenic
0.55
D
MetaRNN
Pathogenic
0.96
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
0.90
D
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.79
T
PROVEAN
Uncertain
-3.6
D;D;.;D;D;D;D;D
REVEL
Pathogenic
0.83
Sift
Uncertain
0.014
D;D;.;D;D;D;D;D
Sift4G
Uncertain
0.0060
D;D;D;D;D;D;D;D
Polyphen
0.90
.;.;.;.;.;P;.;.
Vest4
0.92
MutPred
0.86
Loss of disorder (P = 0.071);Loss of disorder (P = 0.071);.;Loss of disorder (P = 0.071);Loss of disorder (P = 0.071);Loss of disorder (P = 0.071);.;.;
MVP
0.99
MPC
2.1
ClinPred
0.98
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
gMVP
0.98

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1131692042; hg19: chrX-153628144; API