chrX-154400825-C-A

Variant names:

• chrX-154400825-C-A
• rs387906727
• NM_006013.5:c.616C>A

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.616C>A​(p.Leu206Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,900 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: RPL10 NM_006013.5 missense
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 1.54
• Publications: 6 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]

RPL10 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked, syndromic, 35

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: DEFINITIVE 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: XL, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

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, 0.919

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.616C>A	p.Leu206Met	missense	Exon 7 of 7	NP_006004.3	X5D2T3
	RPL10	NM_001303624.2		c.616C>A	p.Leu206Met	missense	Exon 6 of 6	NP_001290553.1	P27635
	RPL10	NM_001303625.1		c.616C>A	p.Leu206Met	missense	Exon 7 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.616C>A	p.Leu206Met	missense	Exon 7 of 7	ENSP00000358832.2	P27635
	RPL10	ENST00000344746.8	TSL:1	c.616C>A	p.Leu206Met	missense	Exon 6 of 6	ENSP00000341730.4	P27635
	RPL10	ENST00000458500.5	TSL:1	c.453C>A	p.Leu151Leu	synonymous	Exon 6 of 6	ENSP00000395025.1	A6QRI9

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000566 AC: 1 AN: 176756 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000128

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097900 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363302

African (AFR) AF: 0.00 AC: 0 AN: 26396

American (AMR) AF: 0.00 AC: 0 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40323

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 842056

Other (OTH) AF: 0.00 AC: 0 AN: 46091

GnomAD4 genome Cov.: 23

ExAC AF: 0.00000826 AC: 1

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Autism, susceptibility to, X-linked 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.043	D
PhyloP100		1.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.60
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.0080	D
Vest4		0.85
MutPred		0.91		Gain of MoRF binding (P = 0.054)
MVP		0.95
MPC		1.8
ClinPred		0.96	D
GERP RS		0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.86
Mutation Taster		=4/96	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

dbSNP: rs387906727; hg19: chrX-153629166;