16-1772972-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_023936.2(MRPS34):​c.148C>A​(p.Leu50Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 35)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MRPS34
NM_023936.2 missense

Scores

5
6
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.80
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.757

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPS34NM_023936.2 linkc.148C>A p.Leu50Met missense_variant Exon 1 of 3 ENST00000397375.7 NP_076425.1 P82930
EME2NM_001257370.2 linkc.-256G>T 5_prime_UTR_variant Exon 1 of 8 ENST00000568449.7 NP_001244299.1 A4GXA9-1
MRPS34NM_001300900.2 linkc.148C>A p.Leu50Met missense_variant Exon 1 of 3 NP_001287829.1 P82930C9JJ19

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPS34ENST00000397375.7 linkc.148C>A p.Leu50Met missense_variant Exon 1 of 3 1 NM_023936.2 ENSP00000380531.3 P82930
MRPS34ENST00000177742.7 linkc.148C>A p.Leu50Met missense_variant Exon 1 of 3 1 ENSP00000177742.3 C9JJ19
EME2ENST00000568449 linkc.-256G>T 5_prime_UTR_variant Exon 1 of 8 1 NM_001257370.2 ENSP00000457353.1 A4GXA9-1

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1296440
Hom.:
0
Cov.:
63
AF XY:
0.00
AC XY:
0
AN XY:
633992
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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.:
35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Uncertain
0.045
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
T;T
Eigen
Uncertain
0.28
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.64
T;T
M_CAP
Pathogenic
0.79
D
MetaRNN
Pathogenic
0.76
D;D
MetaSVM
Benign
-0.49
T
MutationAssessor
Uncertain
2.4
.;M
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
0.010
N;N
REVEL
Uncertain
0.33
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.61
MutPred
0.58
Gain of MoRF binding (P = 0.076);Gain of MoRF binding (P = 0.076);
MVP
0.45
MPC
2.7
ClinPred
0.98
D
GERP RS
2.8
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.1
Varity_R
0.27
gMVP
0.66

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: rs964367525; hg19: chr16-1822973; API