GeneBe

chrX-139561500-TA-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000133.4(F9):​c.839-20delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000931 in 1,073,939 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 9.3e-7 ( 0 hom. 0 hem. )

Consequence

F9
NM_000133.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.270

Publications

0 publications found
Variant links:
Genes affected
F9 (HGNC:3551): (coagulation factor IX) This gene encodes vitamin K-dependent coagulation factor IX that circulates in the blood as an inactive zymogen. This factor is converted to an active form by factor XIa, which excises the activation peptide and thus generates a heavy chain and a light chain held together by one or more disulfide bonds. The role of this activated factor IX in the blood coagulation cascade is to activate factor X to its active form through interactions with Ca+2 ions, membrane phospholipids, and factor VIII. Alterations of this gene, including point mutations, insertions and deletions, cause factor IX deficiency, which is a recessive X-linked disorder, also called hemophilia B or Christmas disease. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Sep 2015]
F9 Gene-Disease associations (from GenCC):
  • hemophilia B
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
  • mild hemophilia B
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • moderately severe hemophilia B
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • severe hemophilia B
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • symptomatic form of hemophilia B in female carriers
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • thrombophilia, X-linked, due to factor 9 defect
    Inheritance: XL Classification: LIMITED Submitted by: ClinGen

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
F9NM_000133.4 linkc.839-20delA intron_variant Intron 7 of 7 ENST00000218099.7 NP_000124.1 P00740-1
F9NM_001313913.2 linkc.725-20delA intron_variant Intron 6 of 6 NP_001300842.1 P00740-2
F9XM_005262397.5 linkc.710-20delA intron_variant Intron 6 of 6 XP_005262454.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
F9ENST00000218099.7 linkc.839-23delA intron_variant Intron 7 of 7 1 NM_000133.4 ENSP00000218099.2 P00740-1
F9ENST00000394090.2 linkc.725-23delA intron_variant Intron 6 of 6 1 ENSP00000377650.2 P00740-2
F9ENST00000643157.1 linkn.1506-23delA intron_variant Intron 5 of 6

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
9.31e-7
AC:
1
AN:
1073939
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
342587
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
25925
American (AMR)
AF:
0.00
AC:
0
AN:
34607
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18955
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30065
South Asian (SAS)
AF:
0.00
AC:
0
AN:
52206
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40338
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4024
European-Non Finnish (NFE)
AF:
0.00000122
AC:
1
AN:
822562
Other (OTH)
AF:
0.00
AC:
0
AN:
45257
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.27
BranchPoint Hunter
4.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs773613916; hg19: chrX-138643659; API