Genetic Variant MRPL13:p.Ala15Val (chr8-120443292-G-A) – 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_014078.6(MRPL13):c.44C>T(p.Ala15Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000699 in 1,431,332 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. A15G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 30)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MRPL13
NM_014078.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.21

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.44C>T	p.Ala15Val	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.44C>T	p.Ala15Val	missense	Exon 2 of 7	ENSP00000306548.3	Q9BYD1
MRPL13	ENST00000518696.5	TSL:1	n.44C>T		non_coding_transcript_exon	Exon 2 of 6	ENSP00000428867.1	E5RFI2
MRPL13	ENST00000862519.1		c.44C>T	p.Ala15Val	missense	Exon 2 of 8	ENSP00000532578.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

139282

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1431332

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711192

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31988

American (AMR)

AF:

0.00

AC:

AN:

39634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25064

East Asian (EAS)

AF:

0.00

AC:

AN:

38654

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098970

Other (OTH)

AF:

0.00

AC:

AN:

58994

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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

139282

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66428

African (AFR)

AF:

0.00

AC:

AN:

37812

American (AMR)

AF:

0.00

AC:

AN:

12972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3376

East Asian (EAS)

AF:

0.00

AC:

AN:

4852

South Asian (SAS)

AF:

0.00

AC:

AN:

4300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65240

Other (OTH)

AF:

0.00

AC:

AN:

1858

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

Eigen

Benign

0.043

Eigen_PC

Benign

0.036

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.1

PhyloP100

5.2

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.12

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0090

Polyphen

0.58

Vest4

0.47

MutPred

0.34

Loss of MoRF binding (P = 0.1392)

MVP

0.40

MPC

0.41

ClinPred

0.97

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.56

gMVP

0.51

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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