Variant 6-159798056-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014161.5(MRPL18):c.476A>G(p.Lys159Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

MRPL18
NM_014161.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24

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]

MRPL18 links:

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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=0.14366487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL18	NM_014161.5 linkuse as main transcript	c.476A>G	p.Lys159Arg	missense_variant	4/4	ENST00000367034.5	NP_054880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MRPL18	ENST00000367034.5 linkuse as main transcript	c.476A>G	p.Lys159Arg	missense_variant	4/4	1	NM_014161.5	ENSP00000356001	P1
MRPL18	ENST00000476826.5 linkuse as main transcript	n.501A>G		non_coding_transcript_exon_variant	4/4	3
MRPL18	ENST00000480842.1 linkuse as main transcript	n.695A>G		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000360

AC:

AN:

250330

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000262

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461084

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726814

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.476A>G (p.K159R) alteration is located in exon 4 (coding exon 4) of the MRPL18 gene. This alteration results from a A to G substitution at nucleotide position 476, causing the lysine (K) at amino acid position 159 to be replaced by an arginine (R). 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

0.088

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.033

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.72

M_CAP

Benign

0.011

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.64

REVEL

Benign

0.13

Sift

Uncertain

0.011

Sift4G

Benign

0.081

Polyphen

0.56

Vest4

0.17

MutPred

0.34

Loss of ubiquitination at K159 (P = 0.0116);

MVP

0.46

MPC

0.12

ClinPred

0.099

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.078

gMVP

0.69

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over