1-228107769-C-T

Variant summary

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

The NM_181463.3(MRPL55):​c.127G>A​(p.Val43Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MRPL55
NM_181463.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.261
Variant links:
Genes affected
MRPL55 (HGNC:16686): (mitochondrial ribosomal protein L55) 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 39S subunit protein. Multiple transcript variants encoding two different isoforms were identified through sequence analysis. [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=0.19757059).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL55NM_181463.3 linkc.127G>A p.Val43Met missense_variant Exon 4 of 5 ENST00000336520.8 NP_852128.1 Q7Z7F7-1A0A024R3U3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL55ENST00000336520.8 linkc.127G>A p.Val43Met missense_variant Exon 4 of 5 2 NM_181463.3 ENSP00000337342.3 Q7Z7F7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250350
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135754
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460916
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726782
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.235G>A (p.V79M) alteration is located in exon 5 (coding exon 3) of the MRPL55 gene. This alteration results from a G to A substitution at nucleotide position 235, causing the valine (V) at amino acid position 79 to be replaced by a methionine (M). 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
0.15
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
8.5
DANN
Benign
0.97
DEOGEN2
Benign
0.011
T;T;T;T;.;T;T;T;T;T;T;T;T;T;T;T;T;.;.;.
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.093
N
LIST_S2
Benign
0.73
.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;T;T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.14
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.1
M;M;M;M;.;M;M;M;M;M;M;M;M;M;M;M;M;.;.;.
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.63
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.12
Sift
Uncertain
0.022
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.030
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;D
Polyphen
0.45
P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;.;.
Vest4
0.080
MutPred
0.46
Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);.;Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);.;Gain of catalytic residue at V43 (P = 0.0223);Gain of catalytic residue at V43 (P = 0.0223);
MVP
0.12
ClinPred
0.079
T
GERP RS
-0.54
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.092
gMVP
0.086

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1487205388; hg19: chr1-228295470; API