1-27373143-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_003665.4(FCN3):c.386G>A(p.Gly129Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G129S) has been classified as Uncertain significance.
Frequency
Consequence
NM_003665.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FCN3 | NM_003665.4 | c.386G>A | p.Gly129Asp | missense_variant | 5/8 | ENST00000270879.9 | |
FCN3 | NM_173452.3 | c.353G>A | p.Gly118Asp | missense_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FCN3 | ENST00000270879.9 | c.386G>A | p.Gly129Asp | missense_variant | 5/8 | 1 | NM_003665.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250680Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135574
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461434Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727026
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 10, 2022 | The c.386G>A (p.G129D) alteration is located in exon 5 (coding exon 5) of the FCN3 gene. This alteration results from a G to A substitution at nucleotide position 386, causing the glycine (G) at amino acid position 129 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Microcephaly Uncertain:1
Uncertain significance, no assertion criteria provided | research | Department of Pediatrics, Samsung Medical Center, Samsung Medical Center | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at