Genetic Variant RPL13A:p.Val36Leu (chr19-49490249-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012423.4(RPL13A):c.106G>T(p.Val36Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V36I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

RPL13A
NM_012423.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.14

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:

SNORD32A (HGNC:10159): (small nucleolar RNA, C/D box 32A) Predicted to act upstream of or within glucose metabolic process; insulin secretion; and reactive oxygen species metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

SNORD32A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.106G>T	p.Val36Leu	missense	Exon 3 of 8	NP_036555.1	P40429
RPL13A	NM_001270491.2		c.-29-226G>T		intron	N/A	NP_001257420.1	Q8J015
RPL13A	NR_073024.2		n.118G>T		non_coding_transcript_exon	Exon 3 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL13A	ENST00000391857.9	TSL:1 MANE Select	c.106G>T	p.Val36Leu	missense	Exon 3 of 8	ENSP00000375730.4	P40429
RPL13A	ENST00000624069.3	TSL:1	n.96G>T		non_coding_transcript_exon	Exon 3 of 8	ENSP00000485546.1	A0A096LPE0
RPL13A	ENST00000467825.2	TSL:5	c.100G>T	p.Val34Leu	missense	Exon 3 of 8	ENSP00000470037.2	M0QYS1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.60

Eigen

Benign

0.081

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.7

PhyloP100

9.1

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.29

Sift

Benign

0.15

Sift4G

Benign

0.17

Polyphen

0.0050

Vest4

0.75

MutPred

0.66

Loss of sheet (P = 0.0817)

MVP

0.70

MPC

0.49

ClinPred

0.95

GERP RS

4.9

Varity_R

0.20

gMVP

0.79

Mutation Taster

=56/44

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