X-154400601-A-C

Variant names:

• chrX-154400601-A-C
• NM_006013.5:c.467A>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_006013.5(RPL10):​c.467A>C​(p.Lys156Thr) 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: 23)
• Consequence: RPL10 NM_006013.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.69
• Publications: 0 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]

SNORA70 (HGNC:10231): (small nucleolar RNA, H/ACA box 70)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM1: In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 2 uncertain in NM_006013.5
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.883

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL10	NM_006013.5	MANE Select	c.467A>C	p.Lys156Thr	missense	Exon 6 of 7	NP_006004.3	X5D2T3
	RPL10	NM_001303624.2		c.467A>C	p.Lys156Thr	missense	Exon 5 of 6	NP_001290553.1	P27635
	RPL10	NM_001303625.1		c.467A>C	p.Lys156Thr	missense	Exon 6 of 7	NP_001290554.1	P27635

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL10	ENST00000369817.7	TSL:5 MANE Select	c.467A>C	p.Lys156Thr	missense	Exon 6 of 7	ENSP00000358832.2	P27635
	RPL10	ENST00000344746.8	TSL:1	c.467A>C	p.Lys156Thr	missense	Exon 5 of 6	ENSP00000341730.4	P27635
	RPL10	ENST00000458500.5	TSL:1	c.330-101A>C		intron	N/A	ENSP00000395025.1	A6QRI9

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.78	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.59	D
PhyloP100		6.7
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.84
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.049	D
Polyphen		0.80	P
Vest4		0.53
MutPred		0.52		Loss of methylation at K156 (P = 0.0398)
MVP		0.97
MPC		2.8
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
gMVP		0.98
Mutation Taster		=39/61	disease causing

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

Other links and lift over

hg19: chrX-153628942;