3-131462785-G-A
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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
NM_007208.4 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 5.25
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]
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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: {Likely_benign=1, Uncertain_significance=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MRPL3 | NM_007208.4 | c.985C>T | p.Pro329Ser | missense_variant | 10/10 | ENST00000264995.8 | NP_009139.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MRPL3 | ENST00000264995.8 | c.985C>T | p.Pro329Ser | missense_variant | 10/10 | 1 | NM_007208.4 | ENSP00000264995 | P1 | |
MRPL3 | ENST00000425847.6 | c.1066C>T | p.Pro356Ser | missense_variant | 11/11 | 2 | ENSP00000398536 | |||
MRPL3 | ENST00000511168.5 | c.1030C>T | p.Pro344Ser | missense_variant | 10/10 | 2 | ENSP00000424107 | |||
MRPL3 | ENST00000510043.1 | n.409C>T | non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 152118Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000319 AC: 80AN: 250402Hom.: 0 AF XY: 0.000370 AC XY: 50AN XY: 135292
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GnomAD4 exome AF: 0.000167 AC: 244AN: 1460814Hom.: 1 Cov.: 30 AF XY: 0.000183 AC XY: 133AN XY: 726698
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GnomAD4 genome AF: 0.000191 AC: 29AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12AN XY: 74300
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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
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 06, 2024 | Has 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 - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at