Variant 12-93501189-C-T 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_014050.4(MRPL42):c.397C>T(p.Arg133Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000844 in 1,599,272 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 (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

MRPL42
NM_014050.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

Variant links:

Genes affected

MRPL42 (HGNC:14493): (mitochondrial ribosomal protein L42) 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 protein identified as belonging to both the 28S and the 39S subunits. Alternative splicing results in multiple transcript variants. Pseudogenes corresponding to this gene are found on chromosomes 4q, 6p, 6q, 7p, and 15q. [provided by RefSeq, May 2011]

MRPL42 links:

MRPL42 (HGNC:):

MRPL42 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=0.23512563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL42	NM_014050.4 linkuse as main transcript	c.397C>T	p.Arg133Cys	missense_variant	6/6	ENST00000549982.6	NP_054769.1	Q9Y6G3A0A024RBG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL42	ENST00000549982.6 linkuse as main transcript	c.397C>T	p.Arg133Cys	missense_variant	6/6	1	NM_014050.4	ENSP00000449884.1		Q9Y6G3

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000582

AC:

AN:

240584

Hom.:

AF XY:

0.0000614

AC XY:

AN XY:

130266

show subpopulations

Gnomad AFR exome

AF:

0.0000640

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000712

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000993

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000878

AC:

127

AN:

1447240

Hom.:

Cov.:

AF XY:

0.0000973

AC XY:

AN XY:

719650

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000362

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.0000502

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

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 16, 2022

The c.397C>T (p.R133C) alteration is located in exon 6 (coding exon 5) of the MRPL42 gene. This alteration results from a C to T substitution at nucleotide position 397, causing the arginine (R) at amino acid position 133 to be replaced by a cysteine (C). 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

Uncertain

0.090

BayesDel_noAF

Uncertain

0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;T;.

Eigen

Benign

0.091

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.77

.;.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.1

M;M;.

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.9

D;D;D

REVEL

Benign

0.27

Sift

Benign

0.030

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.10

B;B;.

Vest4

0.42

MVP

0.30

MPC

0.13

ClinPred

0.39

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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