17-75020542-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001545.3(MRPL58):​c.421C>A​(p.Arg141Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,613,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

MRPL58
NM_001545.3 missense

Scores

7
10
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.86
Variant links:
Genes affected
MRPL58 (HGNC:5359): (mitochondrial ribosomal protein L58) The protein encoded by this gene is a peptidyl-tRNA hydrolase and a vital component of the large mitochondrial ribosome. The encoded protein serves as a ribosome release factor for this ribosome, which translates mitochondrial genes. This protein may be responsible for degrading prematurely-terminated polypeptides and for reusing stalled ribosomes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL58NM_001545.3 linkc.421C>A p.Arg141Ser missense_variant Exon 5 of 6 ENST00000301585.10 NP_001536.1 Q14197
MRPL58NM_001303265.2 linkc.421C>A p.Arg141Ser missense_variant Exon 5 of 6 NP_001290194.1 Q14197
MRPL58XM_017024574.2 linkc.241C>A p.Arg81Ser missense_variant Exon 5 of 6 XP_016880063.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL58ENST00000301585.10 linkc.421C>A p.Arg141Ser missense_variant Exon 5 of 6 1 NM_001545.3 ENSP00000301585.5 Q14197

Frequencies

GnomAD3 genomes
AF:
0.000191
AC:
29
AN:
152128
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000604
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000479
GnomAD3 exomes
AF:
0.0000676
AC:
17
AN:
251338
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.000741
Gnomad AMR exome
AF:
0.000116
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:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461388
Hom.:
0
Cov.:
32
AF XY:
0.0000124
AC XY:
9
AN XY:
727014
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.0000894
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:
0.00000540
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.000190
AC:
29
AN:
152246
Hom.:
0
Cov.:
31
AF XY:
0.000148
AC XY:
11
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.000602
Gnomad4 AMR
AF:
0.0000654
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:
0.000474
Alfa
AF:
0.0000415
Hom.:
0
Bravo
AF:
0.000212
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000906
AC:
11

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 18, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.421C>A (p.R141S) alteration is located in exon 5 (coding exon 5) of the MRPL58 gene. This alteration results from a C to A substitution at nucleotide position 421, causing the arginine (R) at amino acid position 141 to be replaced by a serine (S). 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
Pathogenic
0.95
BayesDel_addAF
Uncertain
0.021
T
BayesDel_noAF
Pathogenic
0.17
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;T
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Uncertain
0.093
D
MetaRNN
Uncertain
0.63
D;D
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Pathogenic
3.9
.;H
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-5.7
.;D
REVEL
Uncertain
0.63
Sift
Uncertain
0.0010
.;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
.;D
Vest4
0.94
MVP
0.72
MPC
1.1
ClinPred
0.99
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.99
gMVP
0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs151335238; hg19: chr17-73016637; API