rs1557185465

Variant names:

• chrX-154399863-G-A
• rs1557185465
• NM_006013.5:c.251G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-154399863-G-A
• chrX-154399863-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006013.5(RPL10):​c.251G>A​(p.Gly84Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G84G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 24)
• Consequence: RPL10 NM_006013.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.13
• 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]

RPL10 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked, syndromic, 35

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

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.251G>A	p.Gly84Asp	missense	Exon 5 of 7	NP_006004.3	X5D2T3
	RPL10	NM_001256577.2		c.251G>A	p.Gly84Asp	missense	Exon 5 of 6	NP_001243506.2	P27635
	RPL10	NM_001303624.2		c.251G>A	p.Gly84Asp	missense	Exon 4 of 6	NP_001290553.1	P27635

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL10	ENST00000369817.7	TSL:5 MANE Select	c.251G>A	p.Gly84Asp	missense	Exon 5 of 7	ENSP00000358832.2	P27635
	RPL10	ENST00000344746.8	TSL:1	c.251G>A	p.Gly84Asp	missense	Exon 4 of 6	ENSP00000341730.4	P27635
	RPL10	ENST00000458500.5	TSL:1	c.251G>A	p.Gly84Asp	missense	Exon 5 of 6	ENSP00000395025.1	A6QRI9

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions as Germline

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	0.99
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.032	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.47	T
PhyloP100		9.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.51
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.14	T
Polyphen		0.082	B
Vest4		0.87
MutPred		0.42		Loss of MoRF binding (P = 0.0301)
MVP		1.0
MPC		2.2
ClinPred		0.87	D
GERP RS		4.0
PromoterAI		-0.0077	Neutral
gMVP		0.99
Mutation Taster		=59/41	polymorphism

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: rs1557185465; hg19: chrX-153628204;