X-154399826-G-A

Position:

• chrX-154399826-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_006013.5(RPL10):​c.214G>A​(p.Ala72Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: RPL10 NM_006013.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.18

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_006013.5
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL10	NM_006013.5	c.214G>A	p.Ala72Thr	missense_variant	5/7	ENST00000369817.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL10	ENST00000369817.7	c.214G>A	p.Ala72Thr	missense_variant	5/7	5	NM_006013.5	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autism, susceptibility to, X-linked 5;C4478383:Intellectual disability, X-linked, syndromic, 35 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Molecular Genetics Lab, CHRU Brest

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;.;.;.;.;.;T;T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	.;D;D;D;.;D;D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.51	D
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.7	D;D;.;D;D;D;N;D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0020	D;D;.;D;D;D;D;D
Sift4G	Benign	0.074	T;T;T;T;T;T;T;T
Polyphen		0.88	.;.;.;.;.;P;.;.
Vest4		0.58
MutPred		0.67		Loss of MoRF binding (P = 0.1167);Loss of MoRF binding (P = 0.1167);.;Loss of MoRF binding (P = 0.1167);Loss of MoRF binding (P = 0.1167);Loss of MoRF binding (P = 0.1167);.;.;
MVP		0.99
MPC		2.2
ClinPred		0.99	D
GERP RS		4.9
gMVP		0.97

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-153628167; COSMIC: COSV99186288; COSMIC: COSV99186288;