X-54446234-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_004463.3(FGD1):c.2761C>T(p.Arg921Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R921R) has been classified as Likely benign.
Frequency
Consequence
NM_004463.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGD1 | NM_004463.3 | c.2761C>T | p.Arg921Ter | stop_gained | 18/18 | ENST00000375135.4 | |
TSR2 | NM_058163.3 | c.*1684G>A | 3_prime_UTR_variant | 5/5 | ENST00000375151.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGD1 | ENST00000375135.4 | c.2761C>T | p.Arg921Ter | stop_gained | 18/18 | 1 | NM_004463.3 | P1 | |
TSR2 | ENST00000375151.5 | c.*1684G>A | 3_prime_UTR_variant | 5/5 | 1 | NM_058163.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 17, 2023 | De novo variant with confirmed parentage in published literature; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene (Meyer et al., 2021); Nonsense variant predicted to result in protein truncation as the last 31 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34189097, 27551683, 33762894, 33482836) - |
Aarskog syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing;research | Keegan Laboratory, University of Michigan | Mar 15, 2016 | Based on ACMG guidelines, criteria met are PM2, PP1, PP3, and PP4. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at