8-11808693-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001287750.2(FDFT1):c.176G>A(p.Trp59*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000408 in 1,471,840 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 Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001287750.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000145 AC: 2AN: 137548Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000300 AC: 4AN: 1334292Hom.: 0 Cov.: 62 AF XY: 0.00000153 AC XY: 1AN XY: 654734
GnomAD4 genome AF: 0.0000145 AC: 2AN: 137548Hom.: 0 Cov.: 33 AF XY: 0.0000150 AC XY: 1AN XY: 66658
ClinVar
Submissions by phenotype
Squalene synthase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Feb 02, 2022 | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3C. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with squalene synthase deficiency (MIM#618156). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0202 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction), but is located in an exon that may undergo alternative splicing. (I) 0219 - This variant is non-coding in an alternative transcript. This variant is either intronic or in the 5' UTR of all other isoforms of this gene, including the predominant transcript used in ClinVar (UCSC). (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v3) <0.01 for a recessive condition (2 heterozygotes, 0 homozygotes). (SP) 0705 - No comparable NMD-predicted variants in this transcript have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at