16-1772825-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_023936.2(MRPS34):ā€‹c.295C>Gā€‹(p.Arg99Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 1,292,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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 š‘“: 0.0000023 ( 0 hom. )

Consequence

MRPS34
NM_023936.2 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.44
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35603285).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPS34NM_023936.2 linkc.295C>G p.Arg99Gly missense_variant Exon 1 of 3 ENST00000397375.7 NP_076425.1 P82930
EME2NM_001257370.2 linkc.-403G>C 5_prime_UTR_variant Exon 1 of 8 ENST00000568449.7 NP_001244299.1 A4GXA9-1
MRPS34NM_001300900.2 linkc.295C>G p.Arg99Gly 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.295C>G p.Arg99Gly missense_variant Exon 1 of 3 1 NM_023936.2 ENSP00000380531.3 P82930
MRPS34ENST00000177742.7 linkc.295C>G p.Arg99Gly missense_variant Exon 1 of 3 1 ENSP00000177742.3 C9JJ19
EME2ENST00000568449 linkc.-403G>C 5_prime_UTR_variant Exon 1 of 8 1 NM_001257370.2 ENSP00000457353.1 A4GXA9-1

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD3 exomes
AF:
0.0000157
AC:
1
AN:
63734
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
32572
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000387
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000232
AC:
3
AN:
1292424
Hom.:
0
Cov.:
63
AF XY:
0.00000159
AC XY:
1
AN XY:
627840
show subpopulations
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:
0.00000290
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
0.12
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Uncertain
0.19
D
MetaRNN
Benign
0.36
T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Uncertain
2.2
.;M
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-4.4
D;D
REVEL
Benign
0.13
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.0090
D;D
Polyphen
0.90
P;P
Vest4
0.42
MutPred
0.50
Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);
MVP
0.19
MPC
2.8
ClinPred
0.89
D
GERP RS
3.7
Varity_R
0.51
gMVP
0.87

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: rs753841145; hg19: chr16-1822826; API