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GeneBe

3-131462761-C-T

Variant summary

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

The NM_007208.4(MRPL3):c.1009G>A(p.Val337Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,612,458 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

MRPL3
NM_007208.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.127
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=0.08395681).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MRPL3NM_007208.4 linkuse as main transcriptc.1009G>A p.Val337Met missense_variant 10/10 ENST00000264995.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MRPL3ENST00000264995.8 linkuse as main transcriptc.1009G>A p.Val337Met missense_variant 10/101 NM_007208.4 P1
MRPL3ENST00000425847.6 linkuse as main transcriptc.1090G>A p.Val364Met missense_variant 11/112
MRPL3ENST00000511168.5 linkuse as main transcriptc.1054G>A p.Val352Met missense_variant 10/102
MRPL3ENST00000510043.1 linkuse as main transcriptn.433G>A non_coding_transcript_exon_variant 4/42

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000480
AC:
12
AN:
250236
Hom.:
0
AF XY:
0.0000444
AC XY:
6
AN XY:
135240
show subpopulations
Gnomad AFR exome
AF:
0.0000618
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000436
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000438
AC:
64
AN:
1460320
Hom.:
1
Cov.:
30
AF XY:
0.0000509
AC XY:
37
AN XY:
726482
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00126
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000872
Hom.:
0
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000659
AC:
8

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeOct 14, 2022In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with MRPL3-related conditions. This variant is present in population databases (rs141422904, gnomAD 0.05%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 337 of the MRPL3 protein (p.Val337Met). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.42
Cadd
Benign
9.8
Dann
Uncertain
0.98
DEOGEN2
Benign
0.046
T;T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.77
T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.084
T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
1.8
L;.
MutationTaster
Benign
0.95
D;D
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.095
Sift
Benign
0.17
T;T
Sift4G
Benign
0.27
T;T
Polyphen
0.49
P;P
Vest4
0.11
MVP
0.88
MPC
0.078
ClinPred
0.086
T
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.089
gMVP
0.40

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: rs141422904; hg19: chr3-131181605; API