Variant rs137852223 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The ENST00000218099.7(F9):c.169C>G(p.Gln57Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000893 in 112,027 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.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Consequence

F9
ENST00000218099.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.687

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 5 uncertain in ENST00000218099.7

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
F9	NM_000133.4 linkuse as main transcript	c.169C>G	p.Gln57Glu	missense_variant	2/8	ENST00000218099.7	NP_000124.1
F9	NM_001313913.2 linkuse as main transcript	c.169C>G	p.Gln57Glu	missense_variant	2/7		NP_001300842.1
F9	XM_005262397.5 linkuse as main transcript	c.169C>G	p.Gln57Glu	missense_variant	2/7		XP_005262454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F9	ENST00000218099.7 linkuse as main transcript	c.169C>G	p.Gln57Glu	missense_variant	2/8	1	NM_000133.4	ENSP00000218099	P1	P00740-1
F9	ENST00000394090.2 linkuse as main transcript	c.169C>G	p.Gln57Glu	missense_variant	2/7	1		ENSP00000377650		P00740-2
F9	ENST00000479617.2 linkuse as main transcript	n.176C>G		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

112027

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34221

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000893

AC:

AN:

112027

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34221

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Uncertain

0.69

D;.

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.66

T;T

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Uncertain

0.43

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.70

N;N

REVEL

Uncertain

0.56

Sift

Benign

0.13

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.032

B;.

Vest4

0.15

MutPred

0.81

Gain of disorder (P = 0.131);Gain of disorder (P = 0.131);

MVP

0.99

MPC

0.089

ClinPred

0.038

GERP RS

1.4

Varity_R

0.19

gMVP

0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over