2-95090428-C-A

Variant summary

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

The NM_031902.5(MRPS5):​c.1026G>T​(p.Met342Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MRPS5
NM_031902.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.819
Variant links:
Genes affected
MRPS5 (HGNC:14498): (mitochondrial ribosomal protein S5) 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 that belongs to the ribosomal protein S5P family. Pseudogenes corresponding to this gene are found on chromosomes 4q, 5q, and 18q. [provided by RefSeq, Jul 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=0.22798753).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPS5NM_031902.5 linkc.1026G>T p.Met342Ile missense_variant Exon 11 of 12 ENST00000272418.7 NP_114108.1 P82675-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPS5ENST00000272418.7 linkc.1026G>T p.Met342Ile missense_variant Exon 11 of 12 1 NM_031902.5 ENSP00000272418.2 P82675-1
ENSG00000289685ENST00000695456.1 linkn.*1905G>T non_coding_transcript_exon_variant Exon 16 of 17 ENSP00000511928.1
ENSG00000289685ENST00000695456.1 linkn.*1905G>T 3_prime_UTR_variant Exon 16 of 17 ENSP00000511928.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1026G>T (p.M342I) alteration is located in exon 11 (coding exon 11) of the MRPS5 gene. This alteration results from a G to T substitution at nucleotide position 1026, causing the methionine (M) at amino acid position 342 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
17
DANN
Benign
0.90
DEOGEN2
Benign
0.0055
T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.20
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
0.11
N
REVEL
Benign
0.073
Sift
Benign
0.37
T
Sift4G
Benign
0.24
T
Polyphen
0.014
B
Vest4
0.39
MutPred
0.60
Loss of MoRF binding (P = 0.1316);
MVP
0.44
MPC
0.23
ClinPred
0.39
T
GERP RS
4.1
Varity_R
0.087
gMVP
0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-95756173; COSMIC: COSV55534355; API