Genetic Variant SERPINF2:p.Ser26Arg (chr17-1745189-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000934.4(SERPINF2):c.78C>A(p.Ser26Arg) 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 benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S26S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SERPINF2
NM_000934.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.43

Publications

0 publications found

Variant links:

Genes affected

SERPINF2 (HGNC:9075): (serpin family F member 2) This gene encodes a member of the serpin family of serine protease inhibitors. The protein is a major inhibitor of plasmin, which degrades fibrin and various other proteins. Consequently, the proper function of this gene has a major role in regulating the blood clotting pathway. Mutations in this gene result in alpha-2-plasmin inhibitor deficiency, which is characterized by severe hemorrhagic diathesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

SERPINF2 Gene-Disease associations (from GenCC):

alpha-2-plasmin inhibitor deficiency
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

SERPINF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38429335).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000934.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINF2	NM_000934.4	MANE Select	c.78C>A	p.Ser26Arg	missense	Exon 3 of 10	NP_000925.2	P08697-1
SERPINF2	NM_001165920.1		c.78C>A	p.Ser26Arg	missense	Exon 3 of 10	NP_001159392.1	P08697-1
SERPINF2	NM_001165921.2		c.78C>A	p.Ser26Arg	missense	Exon 3 of 9	NP_001159393.1	P08697-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINF2	ENST00000453066.6	TSL:5 MANE Select	c.78C>A	p.Ser26Arg	missense	Exon 3 of 10	ENSP00000402286.2	P08697-1
SERPINF2	ENST00000382061.5	TSL:1	c.78C>A	p.Ser26Arg	missense	Exon 3 of 10	ENSP00000371493.4	P08697-1
SERPINF2	ENST00000883620.1		c.78C>A	p.Ser26Arg	missense	Exon 3 of 11	ENSP00000553679.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1416940

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700904

African (AFR)

AF:

0.00

AC:

AN:

32312

American (AMR)

AF:

0.00

AC:

AN:

37228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25338

East Asian (EAS)

AF:

0.00

AC:

AN:

36992

South Asian (SAS)

AF:

0.00

AC:

AN:

81696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089174

Other (OTH)

AF:

0.00

AC:

AN:

58744

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

CADD

Benign

0.29

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.24

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.38

MutationAssessor

Benign

1.8

PhyloP100

-3.4

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.80

REVEL

Uncertain

0.52

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.012

Polyphen

0.78

Vest4

0.26

MutPred

0.36

Gain of solvent accessibility (P = 0.0367)

MVP

0.72

MPC

0.88

ClinPred

0.50

GERP RS

-4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.081

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over