chrX-139561829-T-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_000133.4(F9):c.1144T>C(p.Cys382Arg) variant causes a missense change involving the alteration of a 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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C382S) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000133.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F9 | NM_000133.4 | c.1144T>C | p.Cys382Arg | missense_variant | 8/8 | ENST00000218099.7 | |
F9 | NM_001313913.2 | c.1030T>C | p.Cys344Arg | missense_variant | 7/7 | ||
F9 | XM_005262397.5 | c.1015T>C | p.Cys339Arg | missense_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F9 | ENST00000218099.7 | c.1144T>C | p.Cys382Arg | missense_variant | 8/8 | 1 | NM_000133.4 | P1 | |
F9 | ENST00000394090.2 | c.1030T>C | p.Cys344Arg | missense_variant | 7/7 | 1 | |||
F9 | ENST00000643157.1 | n.1723+88T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Hereditary factor IX deficiency disease;C2749016:Thrombophilia, X-linked, due to factor 9 defect Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 02, 2023 | ClinVar contains an entry for this variant (Variation ID: 10614). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt F9 protein function. This variant is also known as p.Cys336Arg. This missense change has been observed in individuals with hemophilia B (PMID: 19699296). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 382 of the F9 protein (p.Cys382Arg). - |
Hereditary factor IX deficiency disease Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 1989 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at