chr3-131468099-A-G
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_007208.4(MRPL3):c.886T>C(p.Leu296=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,561,654 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 26 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 13 hom. )
Consequence
MRPL3
NM_007208.4 synonymous
NM_007208.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.30
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 3-131468099-A-G is Benign according to our data. Variant chr3-131468099-A-G is described in ClinVar as [Benign]. Clinvar id is 380562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.3 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1605/152148) while in subpopulation AFR AF= 0.0352 (1462/41544). AF 95% confidence interval is 0.0337. There are 26 homozygotes in gnomad4. There are 781 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 26 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRPL3 | NM_007208.4 | c.886T>C | p.Leu296= | synonymous_variant | 9/10 | ENST00000264995.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPL3 | ENST00000264995.8 | c.886T>C | p.Leu296= | synonymous_variant | 9/10 | 1 | NM_007208.4 | P1 | |
MRPL3 | ENST00000425847.6 | c.967T>C | p.Leu323= | synonymous_variant | 10/11 | 2 | |||
MRPL3 | ENST00000511168.5 | c.931T>C | p.Leu311= | synonymous_variant | 9/10 | 2 | |||
MRPL3 | ENST00000510043.1 | n.310T>C | non_coding_transcript_exon_variant | 3/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0105 AC: 1603AN: 152030Hom.: 26 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1603
AN:
152030
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00277 AC: 595AN: 214418Hom.: 10 AF XY: 0.00228 AC XY: 266AN XY: 116838
GnomAD3 exomes
AF:
AC:
595
AN:
214418
Hom.:
AF XY:
AC XY:
266
AN XY:
116838
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00111 AC: 1559AN: 1409506Hom.: 13 Cov.: 27 AF XY: 0.00105 AC XY: 739AN XY: 701730
GnomAD4 exome
AF:
AC:
1559
AN:
1409506
Hom.:
Cov.:
27
AF XY:
AC XY:
739
AN XY:
701730
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0105 AC: 1605AN: 152148Hom.: 26 Cov.: 32 AF XY: 0.0105 AC XY: 781AN XY: 74402
GnomAD4 genome
?
AF:
AC:
1605
AN:
152148
Hom.:
Cov.:
32
AF XY:
AC XY:
781
AN XY:
74402
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
7
AN:
3460
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at