Genetic Variant MRPL13:p.Thr13Ala (chr8-120443299-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_014078.6(MRPL13):c.37A>G(p.Thr13Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MRPL13
NM_014078.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.47

Publications

0 publications found

Variant links:

Genes affected

MRPL13 (HGNC:14278): (mitochondrial ribosomal protein L13) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. [provided by RefSeq, Jul 2008]

MRPL13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.763

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014078.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL13	NM_014078.6	MANE Select	c.37A>G	p.Thr13Ala	missense	Exon 2 of 7	NP_054797.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPL13	ENST00000306185.8	TSL:1 MANE Select	c.37A>G	p.Thr13Ala	missense	Exon 2 of 7	ENSP00000306548.3	Q9BYD1
MRPL13	ENST00000518696.5	TSL:1	n.37A>G		non_coding_transcript_exon	Exon 2 of 6	ENSP00000428867.1	E5RFI2
MRPL13	ENST00000862519.1		c.37A>G	p.Thr13Ala	missense	Exon 2 of 8	ENSP00000532578.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1422136

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

706140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31382

American (AMR)

AF:

0.00

AC:

AN:

36686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24450

East Asian (EAS)

AF:

0.00

AC:

AN:

38730

South Asian (SAS)

AF:

0.00

AC:

AN:

78216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5544

European-Non Finnish (NFE)

AF:

9.12e-7

AC:

AN:

1096206

Other (OTH)

AF:

0.00

AC:

AN:

58600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

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

0.20

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.72

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.31

MutationAssessor

Benign

1.2

PhyloP100

7.5

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-4.2

REVEL

Uncertain

0.42

Sift

Uncertain

0.013

Sift4G

Benign

0.076

Polyphen

1.0

Vest4

0.72

MutPred

0.35

Gain of catalytic residue at Q10 (P = 0.0761)

MVP

0.80

MPC

0.58

ClinPred

0.98

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.72

gMVP

0.54

Mutation Taster

=42/58

disease causing

(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