chr3-15065074-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022497.5(MRPS25):​c.121G>T​(p.Gly41Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MRPS25
NM_022497.5 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06
Variant links:
Genes affected
MRPS25 (HGNC:14511): (mitochondrial ribosomal protein S25) 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. A pseudogene corresponding to this gene is found on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29708397).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MRPS25NM_022497.5 linkuse as main transcriptc.121G>T p.Gly41Cys missense_variant 1/4 ENST00000253686.7
MRPS25NR_135246.2 linkuse as main transcriptn.242G>T non_coding_transcript_exon_variant 1/5
MRPS25NR_135247.2 linkuse as main transcriptn.242G>T non_coding_transcript_exon_variant 1/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MRPS25ENST00000253686.7 linkuse as main transcriptc.121G>T p.Gly41Cys missense_variant 1/41 NM_022497.5 P1P82663-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.92e-7
AC:
1
AN:
1444746
Hom.:
0
Cov.:
31
AF XY:
0.00000139
AC XY:
1
AN XY:
717524
show subpopulations
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:
9.05e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 13, 2023The c.121G>T (p.G41C) alteration is located in exon 1 (coding exon 1) of the MRPS25 gene. This alteration results from a G to T substitution at nucleotide position 121, causing the glycine (G) at amino acid position 41 to be replaced by a cysteine (C). 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
Benign
0.25
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.033
T;.;.
Eigen
Uncertain
0.23
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.30
T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.4
L;L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Uncertain
0.37
Sift
Benign
0.039
D;D;D
Sift4G
Uncertain
0.041
D;D;D
Polyphen
0.98
D;.;.
Vest4
0.45
MutPred
0.28
Loss of disorder (P = 0.0041);Loss of disorder (P = 0.0041);Loss of disorder (P = 0.0041);
MVP
0.11
MPC
0.86
ClinPred
0.93
D
GERP RS
2.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.32
gMVP
0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-15106581; API