rs764159372
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The ENST00000306749.4(FASN):āc.3829C>Gā(p.Pro1277Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,561,396 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1277R) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000306749.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.3829C>G | p.Pro1277Ala | missense_variant | 23/43 | ENST00000306749.4 | NP_004095.4 | |
FASN | XM_011523538.3 | c.3829C>G | p.Pro1277Ala | missense_variant | 23/43 | XP_011521840.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.3829C>G | p.Pro1277Ala | missense_variant | 23/43 | 1 | NM_004104.5 | ENSP00000304592 | P1 | |
FASN | ENST00000634990.1 | c.3823C>G | p.Pro1275Ala | missense_variant | 23/43 | 5 | ENSP00000488964 |
Frequencies
GnomAD3 genomes AF: 0.000217 AC: 33AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00152 AC: 253AN: 166848Hom.: 1 AF XY: 0.00117 AC XY: 106AN XY: 90698
GnomAD4 exome AF: 0.000216 AC: 304AN: 1409078Hom.: 2 Cov.: 66 AF XY: 0.000180 AC XY: 125AN XY: 695702
GnomAD4 genome AF: 0.000217 AC: 33AN: 152318Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Oct 21, 2022 | This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.2% (33/15288) (https://gnomad.broadinstitute.org/variant/17-82085775-G-C?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:462045). This variant amino acid Alanine (Ala) is present in several species including multiple mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
FASN-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 27, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Epileptic encephalopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at