chr5-131180118-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_181705.4(LYRM7):c.42G>A(p.Leu14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 1,611,338 control chromosomes in the GnomAD database, including 1,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.031 ( 95 hom., cov: 30)
Exomes 𝑓: 0.039 ( 1341 hom. )
Consequence
LYRM7
NM_181705.4 synonymous
NM_181705.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.07
Genes affected
LYRM7 (HGNC:28072): (LYR motif containing 7) Inner mitochondrial membrane complex III (CIII) is the main enzyme complex in the mitochondrial respiratory chain, and Rieske Fe-S protein (UQCRFS1) is the last catalytic subunit added to the complex. The protein encoded by this gene is a nuclear-encoded mitochondrial matrix protein that stabilizes UQCRFS1 and chaperones it to the CIII complex. Defects in this gene are a cause of mitochondrial complex III deficiency, nuclear type 8. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]
HINT1 (HGNC:4912): (histidine triad nucleotide binding protein 1) This gene encodes a protein that hydrolyzes purine nucleotide phosphoramidates substrates, including AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester, and AMP-NH2. The encoded protein interacts with these substrates via a histidine triad motif. This gene is considered a tumor suppressor gene. In addition, mutations in this gene can cause autosomal recessive neuromyotonia and axonal neuropathy. There are several related pseudogenes on chromosome 7. Several transcript variants have been observed. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant 5-131180118-G-A is Benign according to our data. Variant chr5-131180118-G-A is described in ClinVar as [Benign]. Clinvar id is 380079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-131180118-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.07 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0313 (4764/152112) while in subpopulation NFE AF= 0.0456 (3102/68004). AF 95% confidence interval is 0.0443. There are 95 homozygotes in gnomad4. There are 2330 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 95 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LYRM7 | NM_181705.4 | c.42G>A | p.Leu14= | synonymous_variant | 2/5 | ENST00000379380.9 | |
LYRM7 | NM_001293735.2 | c.42G>A | p.Leu14= | synonymous_variant | 2/4 | ||
LYRM7 | NR_121658.2 | n.119G>A | non_coding_transcript_exon_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LYRM7 | ENST00000379380.9 | c.42G>A | p.Leu14= | synonymous_variant | 2/5 | 1 | NM_181705.4 | P1 | |
LYRM7 | ENST00000507584.1 | c.42G>A | p.Leu14= | synonymous_variant | 2/4 | 2 | |||
LYRM7 | ENST00000510516.5 | c.42G>A | p.Leu14= | synonymous_variant | 2/3 | 2 | |||
HINT1 | ENST00000506207.2 | n.109-8385C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0313 AC: 4764AN: 151994Hom.: 95 Cov.: 30
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GnomAD3 exomes AF: 0.0338 AC: 8461AN: 250584Hom.: 234 AF XY: 0.0349 AC XY: 4723AN XY: 135488
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GnomAD4 exome AF: 0.0391 AC: 57011AN: 1459226Hom.: 1341 Cov.: 28 AF XY: 0.0389 AC XY: 28227AN XY: 726062
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GnomAD4 genome ? AF: 0.0313 AC: 4764AN: 152112Hom.: 95 Cov.: 30 AF XY: 0.0313 AC XY: 2330AN XY: 74366
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 22, 2016 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 04, 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. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at