16-1772860-C-T

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

Scores

4
1
2

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 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
MRPS34NM_023936.2 linkc.260G>A p.Trp87* stop_gained Exon 1 of 3 ENST00000397375.7 NP_076425.1 P82930
EME2NM_001257370.2 linkc.-368C>T 5_prime_UTR_variant Exon 1 of 8 ENST00000568449.7 NP_001244299.1 A4GXA9-1
MRPS34NM_001300900.2 linkc.260G>A p.Trp87* stop_gained 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>A p.Trp87* stop_gained Exon 1 of 3 1 NM_023936.2 ENSP00000380531.3 P82930
MRPS34ENST00000177742.7 linkc.260G>A p.Trp87* stop_gained Exon 1 of 3 1 ENSP00000177742.3 C9JJ19
EME2ENST00000568449 linkc.-368C>T 5_prime_UTR_variant Exon 1 of 8 1 NM_001257370.2 ENSP00000457353.1 A4GXA9-1

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1295224
Hom.:
0
Cov.:
63
AF XY:
0.00
AC XY:
0
AN XY:
630062
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:
0.00
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
BayesDel_addAF
Pathogenic
0.51
D
BayesDel_noAF
Pathogenic
0.50
CADD
Pathogenic
44
DANN
Uncertain
0.99
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Benign
0.74
D
Vest4
0.062
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs947756957; hg19: chr16-1822861; API