X-154400481-G-T

Variant names:

• chrX-154400481-G-T
• rs2068007021
• NM_006013.5:c.347G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006013.5(RPL10):​c.347G>T​(p.Arg116Leu) variant causes a missense 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. 11/19 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R116Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: RPL10 NM_006013.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.96
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

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.347G>T	p.Arg116Leu	missense	Exon 6 of 7	NP_006004.3	X5D2T3
	RPL10	NM_001303624.2		c.347G>T	p.Arg116Leu	missense	Exon 5 of 6	NP_001290553.1	P27635
	RPL10	NM_001303625.1		c.347G>T	p.Arg116Leu	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.347G>T	p.Arg116Leu	missense	Exon 6 of 7	ENSP00000358832.2	P27635
	RPL10	ENST00000344746.8	TSL:1	c.347G>T	p.Arg116Leu	missense	Exon 5 of 6	ENSP00000341730.4	P27635
	RPL10	ENST00000458500.5	TSL:1	c.330-221G>T		intron	N/A	ENSP00000395025.1	A6QRI9

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.18e-7 AC: 1 AN: 1089500 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 360298

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26362

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54104

European-Finnish (FIN) AF: 0.0000303 AC: 1 AN: 32987

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3322

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841980

Other (OTH) AF: 0.00 AC: 0 AN: 45952

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.65	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.33	D
PhyloP100		9.0
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-6.3	D
REVEL	Pathogenic	0.78
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.0	B
Vest4		0.80
MutPred		0.73		Loss of MoRF binding (P = 0.0074)
MVP		0.99
MPC		2.0
ClinPred		1.0	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.94
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2068007021; hg19: chrX-153628822;