rs781184105

Variant names:

• chrX-139530790-C-A
• NM_000133.4:c.26C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-139530790-C-A
• chrX-139530790-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000133.4(F9):​c.26C>A​(p.Ala9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: F9 NM_000133.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
F9	NM_000133.4	c.26C>A	p.Ala9Glu	missense_variant	Exon 1 of 8	ENST00000218099.7	NP_000124.1
F9	NM_001313913.2	c.26C>A	p.Ala9Glu	missense_variant	Exon 1 of 7		NP_001300842.1
F9	XM_005262397.5	c.26C>A	p.Ala9Glu	missense_variant	Exon 1 of 7		XP_005262454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F9	ENST00000218099.7	c.26C>A	p.Ala9Glu	missense_variant	Exon 1 of 8	1	NM_000133.4	ENSP00000218099.2
F9	ENST00000394090.2	c.26C>A	p.Ala9Glu	missense_variant	Exon 1 of 7	1		ENSP00000377650.2
F9	ENST00000479617.2	n.33C>A		non_coding_transcript_exon_variant	Exon 1 of 4	5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D;.
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.76	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.50
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.019	D;D
Polyphen		0.95	P;.
Vest4		0.48
MutPred		0.50		Gain of disorder (P = 0.0214);Gain of disorder (P = 0.0214);
MVP		0.94
MPC		0.099
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.59
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-138612949;