dbSNP rs1452885468: MRPS34:p.Arg53Leu (chr16-1772962-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_023936.2(MRPS34):c.158G>T(p.Arg53Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R53Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MRPS34
NM_023936.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.87

Publications

0 publications found

Variant links:

Genes affected

MRPS34 (HGNC:16618): (mitochondrial ribosomal protein S34) 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 28S subunit protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

MRPS34 links:

EME2 (HGNC:27289): (essential meiotic structure-specific endonuclease subunit 2) EME2 forms a heterodimer with MUS81 (MIM 606591) that functions as an XPF (MIM 278760)-type flap/fork endonuclease in DNA repair (Ciccia et al., 2007 [PubMed 17289582]).[supplied by OMIM, Mar 2008]

EME2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055558294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS34	NM_023936.2 link	c.158G>T	p.Arg53Leu	missense_variant	Exon 1 of 3	ENST00000397375.7	NP_076425.1	P82930
EME2	NM_001257370.2 link	c.-266C>A		5_prime_UTR_variant	Exon 1 of 8	ENST00000568449.7	NP_001244299.1	A4GXA9-1
MRPS34	NM_001300900.2 link	c.158G>T	p.Arg53Leu	missense_variant	Exon 1 of 3		NP_001287829.1	P82930C9JJ19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MRPS34	ENST00000397375.7 link	c.158G>T	p.Arg53Leu	missense_variant	Exon 1 of 3	1	NM_023936.2	ENSP00000380531.3	P82930
MRPS34	ENST00000177742.7 link	c.158G>T	p.Arg53Leu	missense_variant	Exon 1 of 3	1		ENSP00000177742.3	C9JJ19
EME2	ENST00000568449.7 link	c.-266C>A		5_prime_UTR_variant	Exon 1 of 8	1	NM_001257370.2	ENSP00000457353.1	A4GXA9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

53122

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1296724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

634208

African (AFR)

AF:

0.00

AC:

AN:

25322

American (AMR)

AF:

0.00

AC:

AN:

20498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19426

East Asian (EAS)

AF:

0.00

AC:

AN:

30870

South Asian (SAS)

AF:

0.00

AC:

AN:

65878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40032

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4954

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1036230

Other (OTH)

AF:

0.00

AC:

AN:

53514

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0027

T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.84

T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.92

.;L

PhyloP100

1.9

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.52

N;N

REVEL

Benign

0.043

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0040

B;B

Vest4

0.099

MutPred

0.35

Gain of catalytic residue at R53 (P = 0.0023);Gain of catalytic residue at R53 (P = 0.0023);

MVP

0.27

MPC

3.1

ClinPred

0.57

GERP RS

2.7

PromoterAI

-0.065

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

Varity_R

0.051

gMVP

0.71

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over