chr1-27373135-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003665.4(FCN3):c.393+1G>A variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,613,542 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003665.4 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FCN3 | NM_003665.4 | c.393+1G>A | splice_donor_variant | ENST00000270879.9 | |||
FCN3 | NM_173452.3 | c.360+1G>A | splice_donor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FCN3 | ENST00000270879.9 | c.393+1G>A | splice_donor_variant | 1 | NM_003665.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000953 AC: 145AN: 152154Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000259 AC: 65AN: 250510Hom.: 1 AF XY: 0.000155 AC XY: 21AN XY: 135470
GnomAD4 exome AF: 0.0000992 AC: 145AN: 1461270Hom.: 0 Cov.: 32 AF XY: 0.0000839 AC XY: 61AN XY: 726956
GnomAD4 genome ? AF: 0.000952 AC: 145AN: 152272Hom.: 1 Cov.: 32 AF XY: 0.000913 AC XY: 68AN XY: 74452
ClinVar
Submissions by phenotype
FCN3-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 08, 2023 | The FCN3 c.393+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported in an individual with cardiovascular disease trait, however additional clinical details were not provided (Supplemental Table 1, Glicksberg et al. 2019. PubMed ID: 31345219). This variant is reported in 0.31% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-27699626-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at