Genetic Variant RPL10:p.Ser79Ile (chrX-154399848-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006013.5(RPL10):c.236G>T(p.Ser79Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,098,026 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

RPL10
NM_006013.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.30

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL10	NM_006013.5 link	c.236G>T	p.Ser79Ile	missense_variant	Exon 5 of 7	ENST00000369817.7	NP_006004.3	P27635X5D2T3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL10	ENST00000369817.7 link	c.236G>T	p.Ser79Ile	missense_variant	Exon 5 of 7	5	NM_006013.5	ENSP00000358832.2		P27635

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

112546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34688

FAILED QC

Gnomad AFR

AF:

0.00

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:

1098026

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363394

show subpopulations

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:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

112600

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34752

Gnomad4 AFR

AF:

0.00

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

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

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

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

M_CAP

Benign

0.083

MetaRNN

Uncertain

0.53

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

MetaSVM

Benign

-0.62

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.1

N;N;.;N;N;N;N;N

REVEL

Uncertain

0.37

Sift

Benign

0.46

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

Sift4G

Benign

0.41

T;T;T;T;T;T;T;T

Polyphen

0.16, 0.77

.;.;.;.;.;B;P;.

Vest4

0.36

MutPred

0.41

Gain of methylation at K78 (P = 0.0972);Gain of methylation at K78 (P = 0.0972);.;Gain of methylation at K78 (P = 0.0972);Gain of methylation at K78 (P = 0.0972);Gain of methylation at K78 (P = 0.0972);.;.;

MVP

0.97

MPC

2.2

ClinPred

0.90

GERP RS

4.9

gMVP

0.91

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over