8-120432053-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014078.6(MRPL13):ā€‹c.222A>Cā€‹(p.Gln74His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,608,576 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000030 ( 0 hom. )

Consequence

MRPL13
NM_014078.6 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.186
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23397234).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL13NM_014078.6 linkc.222A>C p.Gln74His missense_variant Exon 3 of 7 ENST00000306185.8 NP_054797.2 Q9BYD1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL13ENST00000306185.8 linkc.222A>C p.Gln74His missense_variant Exon 3 of 7 1 NM_014078.6 ENSP00000306548.3 Q9BYD1
MRPL13ENST00000518696.5 linkn.152-6687A>C intron_variant Intron 2 of 5 1 ENSP00000428867.1 E5RFI2
MRPL13ENST00000518918.1 linkc.150A>C p.Gln50His missense_variant Exon 3 of 6 2 ENSP00000430545.1 E5RJI7
MRPL13ENST00000520677.1 linkn.157-6687A>C intron_variant Intron 2 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152130
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000323
AC:
8
AN:
247914
Hom.:
0
AF XY:
0.0000298
AC XY:
4
AN XY:
134084
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000623
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000302
AC:
44
AN:
1456446
Hom.:
0
Cov.:
29
AF XY:
0.0000304
AC XY:
22
AN XY:
724560
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000334
Gnomad4 OTH exome
AF:
0.0000831
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152130
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74308
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:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000509
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000577
AC:
7

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 06, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.222A>C (p.Q74H) alteration is located in exon 3 (coding exon 3) of the MRPL13 gene. This alteration results from a A to C substitution at nucleotide position 222, causing the glutamine (Q) at amino acid position 74 to be replaced by a histidine (H). 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
0.55
BayesDel_addAF
Benign
-0.0072
T
BayesDel_noAF
Uncertain
-0.060
CADD
Benign
20
DANN
Benign
0.83
DEOGEN2
Benign
0.24
T;.
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.23
T;T
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.8
M;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-0.65
N;N
REVEL
Benign
0.20
Sift
Benign
0.47
T;T
Sift4G
Benign
0.29
T;.
Polyphen
0.93
P;.
Vest4
0.79
MutPred
0.42
Gain of disorder (P = 0.079);.;
MVP
0.73
MPC
0.52
ClinPred
0.46
T
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.29
gMVP
0.77

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: rs149721671; hg19: chr8-121444293; API