Menu
GeneBe

3-131462785-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_007208.4(MRPL3):c.985C>T(p.Pro329Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000169 in 1,612,932 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

MRPL3
NM_007208.4 missense

Scores

1
8
10

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 5.25
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.012918562).
BP6
Variant 3-131462785-G-A is Benign according to our data. Variant chr3-131462785-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1203624.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MRPL3NM_007208.4 linkuse as main transcriptc.985C>T p.Pro329Ser missense_variant 10/10 ENST00000264995.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MRPL3ENST00000264995.8 linkuse as main transcriptc.985C>T p.Pro329Ser missense_variant 10/101 NM_007208.4 P1
MRPL3ENST00000425847.6 linkuse as main transcriptc.1066C>T p.Pro356Ser missense_variant 11/112
MRPL3ENST00000511168.5 linkuse as main transcriptc.1030C>T p.Pro344Ser missense_variant 10/102
MRPL3ENST00000510043.1 linkuse as main transcriptn.409C>T non_coding_transcript_exon_variant 4/42

Frequencies

GnomAD3 genomes
AF:
0.000191
AC:
29
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00722
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000319
AC:
80
AN:
250402
Hom.:
0
AF XY:
0.000370
AC XY:
50
AN XY:
135292
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00627
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000884
Gnomad OTH exome
AF:
0.00115
GnomAD4 exome
AF:
0.000167
AC:
244
AN:
1460814
Hom.:
1
Cov.:
30
AF XY:
0.000183
AC XY:
133
AN XY:
726698
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00698
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.000630
GnomAD4 genome
AF:
0.000191
AC:
29
AN:
152118
Hom.:
0
Cov.:
32
AF XY:
0.000162
AC XY:
12
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00722
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000510
Hom.:
0
Bravo
AF:
0.000208
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000198
AC:
24

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxMay 09, 2022Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function -
Likely benign, criteria provided, single submitterclinical testingInvitaeNov 27, 2023- -
not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 28, 2023The c.985C>T (p.P329S) alteration is located in exon 10 (coding exon 10) of the MRPL3 gene. This alteration results from a C to T substitution at nucleotide position 985, causing the proline (P) at amino acid position 329 to be replaced by a serine (S). 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
0.14
BayesDel_addAF
Benign
-0.034
T
BayesDel_noAF
Benign
-0.11
Cadd
Benign
22
Dann
Uncertain
1.0
DEOGEN2
Benign
0.19
T;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.013
T;T
MetaSVM
Benign
-0.34
T
MutationAssessor
Uncertain
2.6
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.48
T
PROVEAN
Pathogenic
-6.1
D;D
REVEL
Benign
0.22
Sift
Uncertain
0.024
D;D
Sift4G
Uncertain
0.041
D;D
Polyphen
0.52
P;P
Vest4
0.28
MVP
0.90
MPC
0.22
ClinPred
0.30
T
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.35
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

LitVar

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

Other links and lift over

dbSNP: rs145183319; hg19: chr3-131181629; COSMIC: COSV53913223; COSMIC: COSV53913223; API