Genetic Variant NM_012423.4:c.8A>G (chr19-49487637-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_012423.4(RPL13A):c.8A>G(p.Glu3Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPL13A
NM_012423.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Publications

0 publications found

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:

ENSG00000273189 (HGNC:):

ENSG00000273189 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2887987).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012423.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL13A	NM_012423.4	MANE Select	c.8A>G	p.Glu3Gly	missense	Exon 1 of 8	NP_036555.1	P40429
RPL13A	NM_001270491.2		c.-100A>G		5_prime_UTR	Exon 1 of 7	NP_001257420.1	Q8J015
RPL13A	NR_073024.2		n.30A>G		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL13A	ENST00000391857.9	TSL:1 MANE Select	c.8A>G	p.Glu3Gly	missense	Exon 1 of 8	ENSP00000375730.4	P40429
RPL13A	ENST00000624069.3	TSL:1	n.8A>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000485546.1	A0A096LPE0
RPL13A	ENST00000467825.2	TSL:5	c.2A>G	p.Glu1Gly	missense	Exon 1 of 8	ENSP00000470037.2	M0QYS1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1419490

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702752

African (AFR)

AF:

0.00

AC:

AN:

31938

American (AMR)

AF:

0.00

AC:

AN:

37536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25150

East Asian (EAS)

AF:

0.00

AC:

AN:

37386

South Asian (SAS)

AF:

0.00

AC:

AN:

80878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091674

Other (OTH)

AF:

0.00

AC:

AN:

58722

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

-0.10

Eigen_PC

Benign

0.024

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.68

M_CAP

Benign

0.014

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.85

MutationAssessor

Benign

2.0

PhyloP100

5.1

PROVEAN

Benign

0.36

REVEL

Benign

0.20

Sift

Benign

0.26

Sift4G

Benign

0.13

Polyphen

0.0070

Vest4

0.51

MutPred

0.42

Loss of stability (P = 0.0376)

MVP

0.41

MPC

0.58

ClinPred

0.63

GERP RS

5.7

PromoterAI

-0.33

Neutral

(source)

Varity_R

0.12

gMVP

0.55

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over