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. 10/14 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

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]

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 id is 589527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-154400842-C-T is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL10	NM_006013.5	c.633C>T	p.Ala211Ala	synonymous_variant	Exon 7 of 7	ENST00000369817.7	NP_006004.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL10	ENST00000369817.7	c.633C>T	p.Ala211Ala	synonymous_variant	Exon 7 of 7	5	NM_006013.5	ENSP00000358832.2

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

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 26379

Gnomad4 AMR exome AF: 0.0000284 AC: 1 AN: 35172

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 19382

Gnomad4 EAS exome AF: 0.0000331 AC: 1 AN: 30193

Gnomad4 SAS exome AF: 0.0112 AC: 606 AN: 53977

Gnomad4 FIN exome AF: 0.0000249 AC: 1 AN: 40230

Gnomad4 NFE exome AF: 0.0000321 AC: 27 AN: 841925

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.000130 AC: 0.000129521 AN: 0.000129521

Gnomad4 AMR AF: 0.000187 AC: 0.000187336 AN: 0.000187336

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00842 AC: 0.00841874 AN: 0.00841874

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000188 AC: 0.0000187977 AN: 0.0000187977

Gnomad4 OTH AF: 0.00130 AC: 0.0012987 AN: 0.0012987

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000162

ExAC AF: 0.00217 AC: 262

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Nov 16, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
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

Publications

LitVar

Other links and lift over

dbSNP: rs371964689; hg19: chrX-153629183;