16-1772888-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_023936.2(MRPS34):​c.232C>G​(p.Arg78Gly) 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)

Consequence

MRPS34
NM_023936.2 missense

Scores

6
10
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.83
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.909

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPS34NM_023936.2 linkc.232C>G p.Arg78Gly missense_variant Exon 1 of 3 ENST00000397375.7 NP_076425.1 P82930
EME2NM_001257370.2 linkc.-340G>C 5_prime_UTR_variant Exon 1 of 8 ENST00000568449.7 NP_001244299.1 A4GXA9-1
MRPS34NM_001300900.2 linkc.232C>G p.Arg78Gly 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.232C>G p.Arg78Gly missense_variant Exon 1 of 3 1 NM_023936.2 ENSP00000380531.3 P82930
MRPS34ENST00000177742.7 linkc.232C>G p.Arg78Gly missense_variant Exon 1 of 3 1 ENSP00000177742.3 C9JJ19
EME2ENST00000568449 linkc.-340G>C 5_prime_UTR_variant Exon 1 of 8 1 NM_001257370.2 ENSP00000457353.1 A4GXA9-1

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
Cov.:
63
GnomAD4 genome
Cov.:
35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.75
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;D
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Pathogenic
0.40
D
MetaRNN
Pathogenic
0.91
D;D
MetaSVM
Benign
-0.75
T
MutationAssessor
Uncertain
2.3
.;M
PrimateAI
Pathogenic
0.92
D
PROVEAN
Pathogenic
-4.9
D;D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
1.0
D;D
Vest4
0.90
MutPred
0.77
Loss of MoRF binding (P = 0.0039);Loss of MoRF binding (P = 0.0039);
MVP
0.21
MPC
3.2
ClinPred
0.99
D
GERP RS
3.7
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.7
Varity_R
0.84
gMVP
0.89

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: rs1410732345; hg19: chr16-1822889; API