8-120419883-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014078.6(MRPL13):​c.362T>A​(p.Met121Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000107 in 1,593,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

MRPL13
NM_014078.6 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.52
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39448223).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL13NM_014078.6 linkc.362T>A p.Met121Lys missense_variant Exon 5 of 7 ENST00000306185.8 NP_054797.2 Q9BYD1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL13ENST00000306185.8 linkc.362T>A p.Met121Lys missense_variant Exon 5 of 7 1 NM_014078.6 ENSP00000306548.3 Q9BYD1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152014
Hom.:
0
Cov.:
32
show subpopulations
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:
0.00316
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000167
AC:
4
AN:
240026
Hom.:
0
AF XY:
0.0000153
AC XY:
2
AN XY:
130358
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000314
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000682
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000912
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000104
AC:
15
AN:
1441840
Hom.:
0
Cov.:
29
AF XY:
0.00000837
AC XY:
6
AN XY:
716978
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000235
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000242
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000998
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152132
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.362T>A (p.M121K) alteration is located in exon 5 (coding exon 5) of the MRPL13 gene. This alteration results from a T to A substitution at nucleotide position 362, causing the methionine (M) at amino acid position 121 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Benign
-0.067
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
22
DANN
Benign
0.68
DEOGEN2
Benign
0.25
T;.
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.39
T;T
MetaSVM
Benign
-0.55
T
MutationAssessor
Pathogenic
3.2
M;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.69
N;N
REVEL
Benign
0.23
Sift
Benign
0.32
T;T
Sift4G
Benign
0.38
T;.
Polyphen
0.043
B;.
Vest4
0.63
MutPred
0.75
Gain of disorder (P = 0.0305);.;
MVP
0.73
MPC
0.24
ClinPred
0.30
T
GERP RS
4.2
Varity_R
0.56
gMVP
0.90

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.

Other links and lift over

dbSNP: rs751147932; hg19: chr8-121432123; API