16-1772860-C-T
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_023936.2(MRPS34):c.260G>A(p.Trp87*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 35)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MRPS34
NM_023936.2 stop_gained
NM_023936.2 stop_gained
Scores
4
1
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.55
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 Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MRPS34 | NM_023936.2 | c.260G>A | p.Trp87* | stop_gained | Exon 1 of 3 | ENST00000397375.7 | NP_076425.1 | |
EME2 | NM_001257370.2 | c.-368C>T | 5_prime_UTR_variant | Exon 1 of 8 | ENST00000568449.7 | NP_001244299.1 | ||
MRPS34 | NM_001300900.2 | c.260G>A | p.Trp87* | stop_gained | Exon 1 of 3 | NP_001287829.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MRPS34 | ENST00000397375.7 | c.260G>A | p.Trp87* | stop_gained | Exon 1 of 3 | 1 | NM_023936.2 | ENSP00000380531.3 | ||
MRPS34 | ENST00000177742.7 | c.260G>A | p.Trp87* | stop_gained | Exon 1 of 3 | 1 | ENSP00000177742.3 | |||
EME2 | ENST00000568449 | c.-368C>T | 5_prime_UTR_variant | Exon 1 of 8 | 1 | NM_001257370.2 | ENSP00000457353.1 |
Frequencies
GnomAD3 genomes Cov.: 35
GnomAD3 genomes
Cov.:
35
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1295224Hom.: 0 Cov.: 63 AF XY: 0.00 AC XY: 0AN XY: 630062
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1295224
Hom.:
Cov.:
63
AF XY:
AC XY:
0
AN XY:
630062
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 35
GnomAD4 genome
Cov.:
35
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Benign
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at