19-49491432-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012423.4(RPL13A):c.410A>G(p.Tyr137Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

RPL13A
NM_012423.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

Variant links:

Genes affected

RPL13A (HGNC:10304): (ribosomal protein L13a) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L13P family of ribosomal proteins that is a component of the 60S subunit. The encoded protein also plays a role in the repression of inflammatory genes as a component of the IFN-gamma-activated inhibitor of translation (GAIT) complex. This gene is co-transcribed with the small nucleolar RNA genes U32, U33, U34, and U35, which are located in the second, fourth, fifth, and sixth introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

RPL13A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059810072).

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RPL13A	NM_012423.4 linkuse as main transcript	c.410A>G	p.Tyr137Cys	missense_variant	7/8	ENST00000391857.9
RPL13A	NM_001270491.2 linkuse as main transcript	c.227A>G	p.Tyr76Cys	missense_variant	6/7
RPL13A	NR_073024.2 linkuse as main transcript	n.422A>G		non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL13A	ENST00000391857.9 linkuse as main transcript	c.410A>G	p.Tyr137Cys	missense_variant	7/8	1	NM_012423.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000182

AC:

AN:

88144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000611

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:

0.0000215

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000976

AC:

AN:

143392

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

77954

show subpopulations

Gnomad AFR exome

AF:

0.000946

Gnomad AMR exome

AF:

0.000243

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000455

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000736

AC:

AN:

502888

Hom.:

Cov.:

AF XY:

0.0000620

AC XY:

AN XY:

257998

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.000255

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000159

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000177

Gnomad4 OTH exome

AF:

0.0000483

GnomAD4 genome

AF:

0.000182

AC:

AN:

88144

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

39608

show subpopulations

Gnomad4 AFR

AF:

0.000611

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:

0.0000215

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000569

Hom.:

ExAC

AF:

0.0000544

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.410A>G (p.Y137C) alteration is located in exon 7 (coding exon 7) of the RPL13A gene. This alteration results from a A to G substitution at nucleotide position 410, causing the tyrosine (Y) at amino acid position 137 to be replaced by a cysteine (C). 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

Benign

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.038

T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.016

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

0.61

PrimateAI

Uncertain

0.76

Sift4G

Benign

0.20

T;T

Polyphen

0.0010

.;B

Vest4

0.53

MutPred

0.38

.;Gain of relative solvent accessibility (P = 0.1259);

MVP

0.72

MPC

0.60

ClinPred

0.022

GERP RS

4.6

Varity_R

0.11

gMVP

0.80

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