6-159797517-C-T

Variant summary

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

The NM_014161.5(MRPL18):​c.470C>T​(p.Ser157Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

MRPL18
NM_014161.5 missense, splice_region

Scores

6
13
Splicing: ADA: 0.3917
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29119742).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL18NM_014161.5 linkc.470C>T p.Ser157Leu missense_variant, splice_region_variant Exon 3 of 4 ENST00000367034.5 NP_054880.2 Q9H0U6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL18ENST00000367034.5 linkc.470C>T p.Ser157Leu missense_variant, splice_region_variant Exon 3 of 4 1 NM_014161.5 ENSP00000356001.4 Q9H0U6
MRPL18ENST00000476826.5 linkn.495C>T splice_region_variant, non_coding_transcript_exon_variant Exon 3 of 4 3
MRPL18ENST00000480842.1 linkn.689C>T splice_region_variant, non_coding_transcript_exon_variant Exon 3 of 4 3
MRPL18ENST00000479638.5 linkn.*113C>T downstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152154
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250770
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135608
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000890
AC:
13
AN:
1460852
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
726628
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152154
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.470C>T (p.S157L) alteration is located in exon 3 (coding exon 3) of the MRPL18 gene. This alteration results from a C to T substitution at nucleotide position 470, causing the serine (S) at amino acid position 157 to be replaced by a leucine (L). 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
0.26
BayesDel_addAF
Benign
-0.082
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.86
D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.29
T
MetaSVM
Benign
-0.79
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.18
Sift
Benign
0.11
T
Sift4G
Benign
0.23
T
Polyphen
0.99
D
Vest4
0.44
MutPred
0.34
Loss of disorder (P = 0.0134);
MVP
0.58
MPC
0.58
ClinPred
0.93
D
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.57
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.39
dbscSNV1_RF
Benign
0.50
SpliceAI score (max)
0.25
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.25
Position offset: 1

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: rs74992920; hg19: chr6-160218549; COSMIC: COSV105109020; COSMIC: COSV105109020; API