Genetic Variant MRPL13:p.Met60Thr (chr8-120432096-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_014078.6(MRPL13):c.179T>C(p.Met60Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,452,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. M60K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MRPL13
NM_014078.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.71

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2835871).

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.179T>C	p.Met60Thr	missense	Exon 3 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.179T>C	p.Met60Thr	missense	Exon 3 of 7	ENSP00000306548.3	Q9BYD1
MRPL13	ENST00000518696.5	TSL:1	n.152-6730T>C		intron	N/A	ENSP00000428867.1	E5RFI2
MRPL13	ENST00000862519.1		c.203T>C	p.Met68Thr	missense	Exon 4 of 8	ENSP00000532578.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000412

AC:

AN:

242936

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000564

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1452192

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33004

American (AMR)

AF:

0.00

AC:

AN:

43502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25852

East Asian (EAS)

AF:

0.0000511

AC:

AN:

39156

South Asian (SAS)

AF:

0.00

AC:

AN:

84020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107786

Other (OTH)

AF:

0.00

AC:

AN:

59958

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.18

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.067

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.77

M_CAP

Benign

0.0032

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

PhyloP100

5.7

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.5

REVEL

Benign

0.23

Sift

Benign

0.20

Sift4G

Benign

0.21

Polyphen

0.023

Vest4

0.71

MutPred

0.73

Gain of catalytic residue at M60 (P = 0.1009)

MVP

0.25

MPC

0.17

ClinPred

0.34

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.68

Mutation Taster

=61/39

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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