11-1995437-C-T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_001400176.1(MRPL23):c.498-16104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: not found (cov: 0)
Failed GnomAD Quality Control
Consequence
MRPL23
NM_001400176.1 intron
NM_001400176.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.82
Genes affected
H19 (HGNC:4713): (H19 imprinted maternally expressed transcript) This gene is located in an imprinted region of chromosome 11 near the insulin-like growth factor 2 (IGF2) gene. This gene is only expressed from the maternally-inherited chromosome, whereas IGF2 is only expressed from the paternally-inherited chromosome. The product of this gene is a long non-coding RNA which functions as a tumor suppressor. Mutations in this gene have been associated with Beckwith-Wiedemann Syndrome and Wilms tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
MRPL23 (HGNC:10322): (mitochondrial ribosomal protein L23) 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. The gene is biallelically expressed, despite its location within a region of imprinted genes on chromosome 11. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 11-1995437-C-T is Benign according to our data. Variant chr11-1995437-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3051583.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MRPL23 | NM_001400176.1 | c.498-16104C>T | intron_variant | Intron 5 of 6 | NP_001387105.1 | |||
MRPL23 | XM_011520273.2 | c.498-16104C>T | intron_variant | Intron 5 of 6 | XP_011518575.1 | |||
H19 | NR_002196.3 | n.2054G>A | non_coding_transcript_exon_variant | Exon 5 of 5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
H19 | ENST00000412788.6 | n.2048G>A | non_coding_transcript_exon_variant | Exon 5 of 5 | 1 | |||||
H19 | ENST00000414790.9 | n.2055G>A | non_coding_transcript_exon_variant | Exon 5 of 5 | 1 | |||||
H19 | ENST00000411861.6 | n.2135G>A | non_coding_transcript_exon_variant | Exon 4 of 4 | 2 |
Frequencies
GnomAD3 genomes Cov.: 0
GnomAD3 genomes
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0
GnomAD3 exomes AF: 0.000223 AC: 51AN: 228746Hom.: 0 AF XY: 0.000111 AC XY: 14AN XY: 126434
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GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSRAC: 0AN: 0Hom.: 0 Cov.: 0AC XY: 0AN XY: 0
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
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3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
H19-related disorder Benign:1
Jul 06, 2022
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at