9-127451659-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001005373.4(LRSAM1):c.-199A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 389,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 0 hom. )
Consequence
LRSAM1
NM_001005373.4 5_prime_UTR
NM_001005373.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.262
Genes affected
LRSAM1 (HGNC:25135): (leucine rich repeat and sterile alpha motif containing 1) This gene encodes a ring finger protein involved in a variety of functions, including regulation of signaling pathways and cell adhesion, mediation of self-ubiquitylation, and involvement in cargo sorting during receptor endocytosis. Mutations in this gene have been associated with Charcot-Marie-Tooth disease. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 9-127451659-A-G is Benign according to our data. Variant chr9-127451659-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 365003.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRSAM1 | NM_001005373.4 | c.-199A>G | 5_prime_UTR_variant | 1/26 | ENST00000300417.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRSAM1 | ENST00000300417.11 | c.-199A>G | 5_prime_UTR_variant | 1/26 | 1 | NM_001005373.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 151728Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000269 AC: 64AN: 237544Hom.: 0 Cov.: 0 AF XY: 0.000281 AC XY: 35AN XY: 124642
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GnomAD4 genome ? AF: 0.000171 AC: 26AN: 151728Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74086
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2015 | 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
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at