19-49491545-A-C

Position:

chr19-49491545-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000391857.9(RPL13A):c.523A>C(p.Met175Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPL13A
ENST00000391857.9 missense, splice_region

Scores

Splicing: ADA: 0.0001752

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12617975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RPL13A	NM_012423.4 linkuse as main transcript	c.523A>C	p.Met175Leu	missense_variant, splice_region_variant	7/8	ENST00000391857.9	NP_036555.1
RPL13A	NM_001270491.2 linkuse as main transcript	c.340A>C	p.Met114Leu	missense_variant, splice_region_variant	6/7		NP_001257420.1
RPL13A	NR_073024.2 linkuse as main transcript	n.535A>C		splice_region_variant, non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL13A	ENST00000391857.9 linkuse as main transcript	c.523A>C	p.Met175Leu	missense_variant, splice_region_variant	7/8	1	NM_012423.4	ENSP00000375730	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151678

Hom.:

Cov.:

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:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000951

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00159

AC:

2193

AN:

1383038

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

1022

AN XY:

683860

show subpopulations

Gnomad4 AFR exome

AF:

0.00135

Gnomad4 AMR exome

AF:

0.0000270

Gnomad4 ASJ exome

AF:

0.000596

Gnomad4 EAS exome

AF:

0.000300

Gnomad4 SAS exome

AF:

0.000588

Gnomad4 FIN exome

AF:

0.0000777

Gnomad4 NFE exome

AF:

0.00188

Gnomad4 OTH exome

AF:

0.000916

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000132

AC:

AN:

151794

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000951

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Jan 17, 2024

The c.523A>C (p.M175L) alteration is located in exon 7 (coding exon 7) of the RPL13A gene. This alteration results from a A to C substitution at nucleotide position 523, causing the methionine (M) at amino acid position 175 to be replaced by a leucine (L). 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

0.081

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.35

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.085

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.53

.;N

REVEL

Benign

0.21

Sift

Benign

0.36

.;T

Sift4G

Benign

0.41

T;T

Polyphen

0.0

.;B

Vest4

0.26

MutPred

0.34

.;Loss of methylation at K170 (P = 0.0687);

MVP

0.46

MPC

0.44

ClinPred

0.97

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.049

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00018

dbscSNV1_RF

Benign

0.0040

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over