NM_014161.5:c.196C>T

Variant summary

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

The NM_014161.5(MRPL18):​c.196C>T​(p.Arg66Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000235 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

MRPL18
NM_014161.5 missense

Scores

5
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59
Variant links:
Genes affected
MRPL18 (HGNC:14477): (mitochondrial ribosomal protein L18) This nuclear gene encodes a protein component of the larger 39S subunit of mitochondrial ribosome. This protein may also aid in the import of nuclear-encoded 5S rRNA into mitochondria. Alternative splicing results in multiple transcript variants, most of which are not predicted to encode a protein. A pseudogene of this gene is found on chromosome 16. [provided by RefSeq, Jan 2016]

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
MRPL18NM_014161.5 linkc.196C>T p.Arg66Trp missense_variant Exon 2 of 4 ENST00000367034.5 NP_054880.2 Q9H0U6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL18ENST00000367034.5 linkc.196C>T p.Arg66Trp missense_variant Exon 2 of 4 1 NM_014161.5 ENSP00000356001.4 Q9H0U6
MRPL18ENST00000476826.5 linkn.221C>T non_coding_transcript_exon_variant Exon 2 of 4 3
MRPL18ENST00000479638.5 linkn.439C>T non_coding_transcript_exon_variant Exon 3 of 4 5
MRPL18ENST00000480842.1 linkn.415C>T non_coding_transcript_exon_variant Exon 2 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152180
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:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250482
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135710
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:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1461878
Hom.:
0
Cov.:
32
AF XY:
0.0000220
AC XY:
16
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000279
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74344
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:
0.0000735
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 31, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.196C>T (p.R66W) alteration is located in exon 2 (coding exon 2) of the MRPL18 gene. This alteration results from a C to T substitution at nucleotide position 196, causing the arginine (R) at amino acid position 66 to be replaced by a tryptophan (W). 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
Benign
0.17
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.27
T
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.026
D
MetaRNN
Uncertain
0.69
D
MetaSVM
Benign
-0.55
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-4.5
D
REVEL
Uncertain
0.35
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.012
D
Polyphen
1.0
D
Vest4
0.72
MVP
0.66
MPC
0.65
ClinPred
1.0
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.56
gMVP
0.68

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: rs369716763; hg19: chr6-160212115; API