Variant X-154399830-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006013.5(RPL10):c.218A>G(p.Asn73Ser) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N73T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

RPL10
NM_006013.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.51

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL10	NM_006013.5 linkuse as main transcript	c.218A>G	p.Asn73Ser	missense_variant	5/7	ENST00000369817.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL10	ENST00000369817.7 linkuse as main transcript	c.218A>G	p.Asn73Ser	missense_variant	5/7	5	NM_006013.5	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1098020

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363422

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Nov 24, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously reported in peer-reviewed literature as pathogenic or benign to our knowledge.; However, in an abstract by Boussard and Ugrasbul-Eksinar (2019), this variant was reported as hemizygous in a patient with intellectual disability with short stature, hypogonadotropic hypogonadism, microcephaly, developmental delay, intellectual disability, and abnormal gait; this indivdual also had a variant in the CUL4B gene (J Endocr Soc. 2019 Apr 15; 3(Suppl 1): SAT-287; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552257/); In an abstract by Laco et al., (2019), this variant was reported as segregating with a neurodevelopmental phenotype with variable additional features in two unrelated families ( Mrio Lao et al. (2019) Medicine (Baltimore). 98 (26):13 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620740/); This variant is associated with the following publications: (PMID: Julie2019[article], Mario2019[abstract]) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

.;.;.;.;.;.;T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

.;D;D;D;.;D;D;D

M_CAP

Pathogenic

0.43

MetaRNN

Pathogenic

0.93

D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.46

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-4.3

D;D;.;D;D;D;D;D

REVEL

Pathogenic

0.66

Sift

Benign

0.040

D;D;.;D;D;D;D;D

Sift4G

Uncertain

0.050

T;T;T;T;T;D;T;D

Polyphen

0.91

.;.;.;.;.;P;.;.

Vest4

0.58

MutPred

0.84

Loss of methylation at K74 (P = 0.1081);Loss of methylation at K74 (P = 0.1081);.;Loss of methylation at K74 (P = 0.1081);Loss of methylation at K74 (P = 0.1081);Loss of methylation at K74 (P = 0.1081);.;.;

MVP

0.96

MPC

1.7

ClinPred

1.0

GERP RS

4.9

gMVP

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.27

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over