rs727502796
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PM4PP3PP5_Moderate
The NM_032228.6(FAR1):c.495_507delinsT(p.Glu165_Pro169delinsAsp) variant causes a protein altering change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
FAR1
NM_032228.6 protein_altering
NM_032228.6 protein_altering
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
FAR1 (HGNC:26222): (fatty acyl-CoA reductase 1) The protein encoded by this gene is required for the reduction of fatty acids to fatty alcohols, a process that is required for the synthesis of monoesters and ether lipids. NADPH is required as a cofactor in this reaction, and 16-18 carbon saturated and unsaturated fatty acids are the preferred substrate. This is a peroxisomal membrane protein, and studies suggest that the N-terminus contains a large catalytic domain located on the outside of the peroxisome, while the C-terminus is exposed to the matrix of the peroxisome. Studies indicate that the regulation of this protein is dependent on plasmalogen levels. Mutations in this gene have been associated with individuals affected by severe intellectual disability, early-onset epilepsy, microcephaly, congenital cataracts, growth retardation, and spasticity (PMID: 25439727). A pseudogene of this gene is located on chromosome 13. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_032228.6.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 11-13708029-AGTAGTCTATCCA-T is Pathogenic according to our data. Variant chr11-13708029-AGTAGTCTATCCA-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 162212.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAR1 | NM_032228.6 | c.495_507delinsT | p.Glu165_Pro169delinsAsp | protein_altering_variant | 4/12 | ENST00000354817.8 | |
FAR1 | XM_011520400.3 | c.495_507delinsT | p.Glu165_Pro169delinsAsp | protein_altering_variant | 4/12 | ||
FAR1 | XM_047427690.1 | c.495_507delinsT | p.Glu165_Pro169delinsAsp | protein_altering_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAR1 | ENST00000354817.8 | c.495_507delinsT | p.Glu165_Pro169delinsAsp | protein_altering_variant | 4/12 | 1 | NM_032228.6 | P1 | |
FAR1 | ENST00000532701.1 | c.495_507delinsT | p.Glu165_Pro169delinsAsp | protein_altering_variant | 4/8 | 2 | |||
FAR1 | ENST00000524933.1 | n.361_373delinsT | non_coding_transcript_exon_variant | 3/4 | 2 | ||||
FAR1 | ENST00000703358.1 | c.495_507delinsT | p.Glu165_Pro169delinsAsp | protein_altering_variant, NMD_transcript_variant | 3/11 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Fatty acyl-CoA reductase 1 deficiency Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 06, 2014 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | May 08, 2023 | Review of the variants reported in Reuter et al., 2017, PMID: 28097321: PS3,PM4,PM3_Supporting,PM2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at