chrX-155022464-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM5PP3_Moderate
The NM_000132.4(F8):c.89A>G(p.Glu30Gly) variant causes a missense 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E30V) has been classified as Pathogenic.
Frequency
Consequence
NM_000132.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F8 | NM_000132.4 | c.89A>G | p.Glu30Gly | missense_variant | 1/26 | ENST00000360256.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F8 | ENST00000360256.9 | c.89A>G | p.Glu30Gly | missense_variant | 1/26 | 1 | NM_000132.4 | P1 | |
F8 | ENST00000453950.1 | c.71A>G | p.Glu24Gly | missense_variant | 2/5 | 3 | |||
F8 | ENST00000423959.5 | c.38+4316A>G | intron_variant | 3 | |||||
F8 | ENST00000647125.1 | c.89A>G | p.Glu30Gly | missense_variant, NMD_transcript_variant | 1/14 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Hereditary factor VIII deficiency disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 19, 2021 | The F8 c.89A>G; p.Glu30Gly variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Additionally, other variants at this codon (c.88G>A, p.Glu30Lys; c.89A>T, p.Glu30Val) have been reported in individuals with mild to moderate hemophilia A and are considered pathogenic (see F8 database and references therein, Abdul-Ghafar 2010). The glutamic acid at codon 30 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.83). However, given the lack of clinical and functional data, the significance of the p.Glu30Gly variant is uncertain at this time. References: Link to F8 database and references therein : https://f8-db.eahad.org/index.php Abdul-Ghafar A et al. Ten novel factor VIII (F8C) mutations in eighteen haemophilia A families detected in Singapore. Haemophilia. 2010 May;16(3):551-3. PMID: 20028422. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.