Variant X-154399836-A-T 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.224A>T(p.Tyr75Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000033 in 1,210,421 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

RPL10
NM_006013.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.68

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:

RPL10 (HGNC:):

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, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL10	NM_006013.5 linkuse as main transcript	c.224A>T	p.Tyr75Phe	missense_variant	5/7	ENST00000369817.7	NP_006004.3	P27635X5D2T3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL10	ENST00000369817.7 linkuse as main transcript	c.224A>T	p.Tyr75Phe	missense_variant	5/7	5	NM_006013.5	ENSP00000358832.2		P27635

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112416

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34556

show subpopulations

Gnomad AFR

AF:

0.0000971

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098005

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363391

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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

AF:

0.0000267

AC:

AN:

112416

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34556

show subpopulations

Gnomad4 AFR

AF:

0.0000971

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.224A>T (p.Y75F) alteration is located in exon 5 (coding exon 4) of the RPL10 gene. This alteration results from a A to T substitution at nucleotide position 224, causing the tyrosine (Y) at amino acid position 75 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

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

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

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

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.88

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

MetaSVM

Uncertain

0.30

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.5

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

REVEL

Pathogenic

0.68

Sift

Benign

0.036

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

Sift4G

Benign

0.064

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

Polyphen

0.36

.;.;.;.;.;B;.;.

Vest4

0.42

MutPred

0.76

Gain of methylation at K74 (P = 0.0262);Gain of methylation at K74 (P = 0.0262);.;Gain of methylation at K74 (P = 0.0262);Gain of methylation at K74 (P = 0.0262);Gain of methylation at K74 (P = 0.0262);.;.;

MVP

0.92

MPC

2.8

ClinPred

0.98

GERP RS

4.9

gMVP

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over