Variant 16-89561665-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000977.4(RPL13):c.334G>T(p.Ala112Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A112T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RPL13
NM_000977.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.82

Variant links:

Genes affected

RPL13 (HGNC:10303): (ribosomal protein L13) 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 ribosomal protein that is a component of the 60S subunit. The protein belongs to the L13E family of ribosomal proteins. It is located in the cytoplasm. This gene is expressed at significantly higher levels in benign breast lesions than in breast carcinomas. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2011]

RPL13 links:

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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
RPL13	NM_000977.4 link	c.334G>T	p.Ala112Ser	missense_variant	Exon 4 of 6	ENST00000311528.10	NP_000968.2	P26373-1A8K4C8
RPL13	NM_033251.2 link	c.334G>T	p.Ala112Ser	missense_variant	Exon 3 of 5		NP_150254.1	P26373-1A8K4C8
RPL13	NM_001243131.1 link	c.267+67G>T		intron_variant	Intron 4 of 6		NP_001230060.1	P26373-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL13	ENST00000311528.10 link	c.334G>T	p.Ala112Ser	missense_variant	Exon 4 of 6	1	NM_000977.4	ENSP00000307889.5		P26373-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250942

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461538

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

T;T;.;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

.;.;D;D

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.8

M;M;.;M

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.84

N;N;.;N

REVEL

Benign

0.17

Sift

Benign

0.099

T;T;.;T

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.17

B;B;.;B

Vest4

0.56

MutPred

0.34

Gain of glycosylation at A112 (P = 0.0495);Gain of glycosylation at A112 (P = 0.0495);Gain of glycosylation at A112 (P = 0.0495);Gain of glycosylation at A112 (P = 0.0495);

MVP

0.63

MPC

0.52

ClinPred

0.92

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.23

gMVP

0.47

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over