rs201060753

Variant summary

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

The NM_007208.4(MRPL3):​c.1021G>T​(p.Gly341Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000683 in 1,611,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

MRPL3
NM_007208.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.314
Variant links:
Genes affected
MRPL3 (HGNC:10379): (mitochondrial ribosomal protein L3) 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 that belongs to the L3P ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 13q. [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=0.11523089).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL3NM_007208.4 linkc.1021G>T p.Gly341Cys missense_variant Exon 10 of 10 ENST00000264995.8 NP_009139.1 P09001

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL3ENST00000264995.8 linkc.1021G>T p.Gly341Cys missense_variant Exon 10 of 10 1 NM_007208.4 ENSP00000264995.2 P09001
MRPL3ENST00000425847.6 linkc.1102G>T p.Gly368Cys missense_variant Exon 11 of 11 2 ENSP00000398536.2 E7ETU7
MRPL3ENST00000511168.5 linkc.1063G>T p.Gly355Cys missense_variant Exon 10 of 10 2 ENSP00000424107.1 H0Y9G6
MRPL3ENST00000510043.1 linkn.445G>T non_coding_transcript_exon_variant Exon 4 of 4 2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152084
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00316
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249736
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
134960
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000685
AC:
10
AN:
1459128
Hom.:
0
Cov.:
30
AF XY:
0.0000124
AC XY:
9
AN XY:
725916
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.00
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
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
7.8
DANN
Benign
0.89
DEOGEN2
Benign
0.068
T;T
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.24
T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.69
N;.
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-2.3
N;N
REVEL
Benign
0.14
Sift
Benign
0.053
T;T
Sift4G
Uncertain
0.038
D;D
Polyphen
0.0020
B;B
Vest4
0.21
MutPred
0.39
.;Gain of catalytic residue at P367 (P = 0.0071);
MVP
0.85
MPC
0.071
ClinPred
0.11
T
GERP RS
0.34
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.31
gMVP
0.34

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: rs201060753; hg19: chr3-131181593; API