chr16-1772956-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_023936.2(MRPS34):c.164G>A(p.Trp55Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000231 in 1,297,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 35)
Exomes 𝑓: 0.0000023 ( 0 hom. )
Consequence
MRPS34
NM_023936.2 stop_gained
NM_023936.2 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 4.33
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 12 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;
PP5
?
Variant 16-1772956-C-T is Pathogenic according to our data. Variant chr16-1772956-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2876971.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRPS34 | NM_023936.2 | c.164G>A | p.Trp55Ter | stop_gained | 1/3 | ENST00000397375.7 | |
EME2 | NM_001257370.2 | c.-272C>T | 5_prime_UTR_variant | 1/8 | ENST00000568449.7 | ||
MRPS34 | NM_001300900.2 | c.164G>A | p.Trp55Ter | stop_gained | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPS34 | ENST00000397375.7 | c.164G>A | p.Trp55Ter | stop_gained | 1/3 | 1 | NM_023936.2 | P1 | |
MRPS34 | ENST00000177742.7 | c.164G>A | p.Trp55Ter | stop_gained | 1/3 | 1 | |||
EME2 | ENST00000568449.7 | c.-272C>T | 5_prime_UTR_variant | 1/8 | 1 | NM_001257370.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 35
GnomAD3 genomes
?
Cov.:
35
GnomAD4 exome AF: 0.00000231 AC: 3AN: 1297392Hom.: 0 Cov.: 62 AF XY: 0.00000158 AC XY: 1AN XY: 634696
GnomAD4 exome
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3
AN:
1297392
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62
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1
AN XY:
634696
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GnomAD4 genome ? Cov.: 35
GnomAD4 genome
?
Cov.:
35
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2023 | This sequence change creates a premature translational stop signal (p.Trp55*) in the MRPS34 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MRPS34 are known to be pathogenic (PMID: 28777931). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MRPS34-related conditions. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at