chr8-139732009-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001160372.4(TRAPPC9):āc.3249C>Gā(p.Phe1083Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000097 in 1,443,764 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. F1083F) has been classified as Likely benign.
Frequency
Consequence
NM_001160372.4 missense
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 |
---|---|---|---|---|---|---|---|
TRAPPC9 | NM_001160372.4 | c.3249C>G | p.Phe1083Leu | missense_variant | 22/23 | ENST00000438773.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAPPC9 | ENST00000438773.4 | c.3249C>G | p.Phe1083Leu | missense_variant | 22/23 | 1 | NM_001160372.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000274 AC: 6AN: 218814Hom.: 0 AF XY: 0.0000339 AC XY: 4AN XY: 117972
GnomAD4 exome AF: 0.00000970 AC: 14AN: 1443764Hom.: 0 Cov.: 32 AF XY: 0.0000126 AC XY: 9AN XY: 716260
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 17, 2023 | The c.3543C>G (p.F1181L) alteration is located in exon 22 (coding exon 22) of the TRAPPC9 gene. This alteration results from a C to G substitution at nucleotide position 3543, causing the phenylalanine (F) at amino acid position 1181 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1181 of the TRAPPC9 protein (p.Phe1181Leu). This variant is present in population databases (rs112551069, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TRAPPC9-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at