chr16-369086-G-C
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_006428.5(MRPL28):c.423C>G(p.Leu141=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,613,754 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0056 ( 5 hom., cov: 34)
Exomes 𝑓: 0.00057 ( 8 hom. )
Consequence
MRPL28
NM_006428.5 synonymous
NM_006428.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.20
Genes affected
MRPL28 (HGNC:14484): (mitochondrial ribosomal protein L28) 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, a part of which was originally isolated by its ability to recognize tyrosinase in an HLA-A24-restricted fashion. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 16-369086-G-C is Benign according to our data. Variant chr16-369086-G-C is described in ClinVar as [Benign]. Clinvar id is 714602.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-2.2 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00563 (858/152268) while in subpopulation AFR AF= 0.019 (790/41536). AF 95% confidence interval is 0.0179. There are 5 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRPL28 | NM_006428.5 | c.423C>G | p.Leu141= | synonymous_variant | 3/6 | ENST00000199706.13 | |
MRPL28 | XM_005255041.3 | c.423C>G | p.Leu141= | synonymous_variant | 3/6 | ||
MRPL28 | XM_011522351.3 | c.423C>G | p.Leu141= | synonymous_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPL28 | ENST00000199706.13 | c.423C>G | p.Leu141= | synonymous_variant | 3/6 | 1 | NM_006428.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00561 AC: 854AN: 152150Hom.: 5 Cov.: 34
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GnomAD3 exomes AF: 0.00138 AC: 347AN: 251094Hom.: 4 AF XY: 0.000980 AC XY: 133AN XY: 135760
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GnomAD4 exome AF: 0.000566 AC: 827AN: 1461486Hom.: 8 Cov.: 30 AF XY: 0.000475 AC XY: 345AN XY: 727048
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 16, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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