1-228107832-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181463.3(MRPL55):​c.64G>A​(p.Ala22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Consequence

MRPL55
NM_181463.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.630
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03590569).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL55NM_181463.3 linkc.64G>A p.Ala22Thr 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.64G>A p.Ala22Thr missense_variant Exon 4 of 5 2 NM_181463.3 ENSP00000337342.3 Q7Z7F7-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152210
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.172G>A (p.A58T) 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 172, causing the alanine (A) at amino acid position 58 to be replaced by a threonine (T). 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
0.071
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
0.36
DANN
Benign
0.65
DEOGEN2
Benign
0.0045
T;T;T;T;.;T;T;T;T;T;T;T;T;T;T;T;T;.;.;.;.
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.030
N
LIST_S2
Benign
0.34
.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;T;T;T;T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.036
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.22
N;N;N;N;.;N;N;N;N;N;N;N;N;N;N;N;N;.;.;.;.
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.45
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;.
REVEL
Benign
0.024
Sift
Benign
1.0
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;.
Sift4G
Benign
0.89
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;.;T;.
Polyphen
0.0030
B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;.;.;.
Vest4
0.048
MutPred
0.36
Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);.;Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);.;Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);Gain of phosphorylation at A22 (P = 0.0305);
MVP
0.12
ClinPred
0.074
T
GERP RS
-8.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.012
gMVP
0.087

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: rs1206394772; hg19: chr1-228295533; API