rs947756957

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023936.2(MRPS34):​c.260G>T​(p.Trp87Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,468 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: 𝑓 0.0000066 ( 0 hom., cov: 35)
Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

MRPS34
NM_023936.2 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.55
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20836368).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPS34NM_023936.2 linkc.260G>T p.Trp87Leu missense_variant Exon 1 of 3 ENST00000397375.7 NP_076425.1 P82930
EME2NM_001257370.2 linkc.-368C>A 5_prime_UTR_variant Exon 1 of 8 ENST00000568449.7 NP_001244299.1 A4GXA9-1
MRPS34NM_001300900.2 linkc.260G>T p.Trp87Leu 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.260G>T p.Trp87Leu missense_variant Exon 1 of 3 1 NM_023936.2 ENSP00000380531.3 P82930
MRPS34ENST00000177742.7 linkc.260G>T p.Trp87Leu missense_variant Exon 1 of 3 1 ENSP00000177742.3 C9JJ19
EME2ENST00000568449 linkc.-368C>A 5_prime_UTR_variant Exon 1 of 8 1 NM_001257370.2 ENSP00000457353.1 A4GXA9-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000156
AC:
1
AN:
64152
Hom.:
0
AF XY:
0.0000297
AC XY:
1
AN XY:
33630
show subpopulations
Gnomad AFR exome
AF:
0.000185
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.72e-7
AC:
1
AN:
1295224
Hom.:
0
Cov.:
63
AF XY:
0.00000159
AC XY:
1
AN XY:
630062
show subpopulations
Gnomad4 AFR exome
AF:
0.0000350
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
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
35
AF XY:
0.0000134
AC XY:
1
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.091
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.034
T;T
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.22
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.85
D;D
M_CAP
Benign
0.066
D
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
.;M
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.077
Sift
Benign
0.20
T;T
Sift4G
Uncertain
0.056
T;T
Polyphen
0.88
P;P
Vest4
0.46
MutPred
0.50
Loss of MoRF binding (P = 0.0298);Loss of MoRF binding (P = 0.0298);
MVP
0.099
MPC
3.3
ClinPred
0.26
T
GERP RS
3.7
Varity_R
0.19
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs947756957; hg19: chr16-1822861; API