chr19-5691922-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004793.4(LONP1):c.*110C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,285,064 control chromosomes in the GnomAD database, including 611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 56 hom., cov: 33)
Exomes 𝑓: 0.028 ( 555 hom. )
Consequence
LONP1
NM_004793.4 3_prime_UTR
NM_004793.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.795
Genes affected
LONP1 (HGNC:9479): (lon peptidase 1, mitochondrial) This gene encodes a mitochondrial matrix protein that belongs to the Lon family of ATP-dependent proteases. This protein mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides in the mitochondrial matrix. It may also have a chaperone function in the assembly of inner membrane protein complexes, and participate in the regulation of mitochondrial gene expression and maintenance of the integrity of the mitochondrial genome. Decreased expression of this gene has been noted in a patient with hereditary spastic paraplegia (PMID:18378094). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]
RPL36 (HGNC:13631): (ribosomal protein L36) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L36E family of ribosomal proteins. It is located in the cytoplasm. Transcript variants derived from alternative splicing exist; they encode the same protein. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 19-5691922-G-A is Benign according to our data. Variant chr19-5691922-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1198795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0222 (3375/152320) while in subpopulation NFE AF= 0.0359 (2440/68038). AF 95% confidence interval is 0.0347. There are 56 homozygotes in gnomad4. There are 1483 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 56 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LONP1 | NM_004793.4 | c.*110C>T | 3_prime_UTR_variant | 18/18 | ENST00000360614.8 | ||
RPL36 | NM_033643.3 | downstream_gene_variant | ENST00000347512.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LONP1 | ENST00000360614.8 | c.*110C>T | 3_prime_UTR_variant | 18/18 | 1 | NM_004793.4 | P1 | ||
RPL36 | ENST00000347512.8 | downstream_gene_variant | 1 | NM_033643.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0222 AC: 3377AN: 152202Hom.: 56 Cov.: 33
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GnomAD4 exome AF: 0.0278 AC: 31450AN: 1132744Hom.: 555 Cov.: 16 AF XY: 0.0271 AC XY: 15276AN XY: 562774
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GnomAD4 genome AF: 0.0222 AC: 3375AN: 152320Hom.: 56 Cov.: 33 AF XY: 0.0199 AC XY: 1483AN XY: 74476
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 29, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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