rs371964689

Variant names:

• chrX-154400842-C-T
• rs371964689
• ENST00000458500.5:c.470C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001256577.2(RPL10):​c.470C>T​(p.Pro157Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000599 in 1,209,786 control chromosomes in the GnomAD database, including 3 homozygotes. There are 333 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., 10 hem., cov: 23)
  • Exomes 𝑓: 0.00063 (3 hom. 323 hem.)
• Consequence: RPL10 NM_001256577.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0510
• Publications: 2 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008334637).
• BP6: Variant X-154400842-C-T is Benign according to our data. Variant chrX-154400842-C-T is described in ClinVar as Benign. ClinVar VariationId is 589527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 10 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256577.2. 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.633C>T	p.Ala211Ala	synonymous	Exon 7 of 7	NP_006004.3	X5D2T3
	RPL10	NM_001256577.2		c.470C>T	p.Pro157Leu	missense	Exon 6 of 6	NP_001243506.2	P27635
	RPL10	NM_001303624.2		c.633C>T	p.Ala211Ala	synonymous	Exon 6 of 6	NP_001290553.1	P27635

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL10	ENST00000458500.5	TSL:1	c.470C>T	p.Pro157Leu	missense	Exon 6 of 6	ENSP00000395025.1	A6QRI9
	RPL10	ENST00000369817.7	TSL:5 MANE Select	c.633C>T	p.Ala211Ala	synonymous	Exon 7 of 7	ENSP00000358832.2	P27635
	RPL10	ENST00000344746.8	TSL:1	c.633C>T	p.Ala211Ala	synonymous	Exon 6 of 6	ENSP00000341730.4	P27635

Frequencies

GnomAD3 genomes AF: 0.000285 AC: 32 AN: 112280 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000188

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00839

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00131

GnomAD2 exomes AF: 0.00179 AC: 303 AN: 169742 AF XY: 0.00274

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: 0.0000678

Gnomad OTH exome AF: 0.00141

GnomAD4 exome AF: 0.000631 AC: 693 AN: 1097453 Hom.: 3 Cov.: 31 AF XY: 0.000890 AC XY: 323 AN XY: 362901

African (AFR) AF: 0.00 AC: 0 AN: 26379

American (AMR) AF: 0.0000284 AC: 1 AN: 35172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30193

South Asian (SAS) AF: 0.0112 AC: 606 AN: 53977

European-Finnish (FIN) AF: 0.0000249 AC: 1 AN: 40230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.0000321 AC: 27 AN: 841925

Other (OTH) AF: 0.00124 AC: 57 AN: 46063

GnomAD4 genome AF: 0.000285 AC: 32 AN: 112333 Hom.: 0 Cov.: 23 AF XY: 0.000290 AC XY: 10 AN XY: 34497

African (AFR) AF: 0.000130 AC: 4 AN: 30883

American (AMR) AF: 0.000187 AC: 2 AN: 10676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.00842 AC: 23 AN: 2732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6183

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53198

Other (OTH) AF: 0.00130 AC: 2 AN: 1540

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000162

ExAC AF: 0.00217 AC: 262

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.5
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0083	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.051
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.083
Sift	Benign	0.053	T
Sift4G	Benign	0.16	T
Polyphen		0.0010	B
MutPred		0.36		Loss of loop (P = 0.0128)
MVP		0.45
ClinPred		0.022	T
GERP RS		-0.68
Mutation Taster		=98/2	polymorphism (auto)

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: rs371964689; hg19: chrX-153629183;