17-1745339-A-C

Variant names:

• chr17-1745339-A-C
• NM_000934.4:c.109A>C
• SERPINF2 p.Ser37Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000934.4(SERPINF2):​c.109A>C​(p.Ser37Arg) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. S37S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 28)
• Consequence: SERPINF2 NM_000934.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 0 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1552527).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINF2	NM_000934.4	MANE Select	c.109A>C	p.Ser37Arg	missense	Exon 4 of 10	NP_000925.2	P08697-1
	SERPINF2	NM_001165920.1		c.109A>C	p.Ser37Arg	missense	Exon 4 of 10	NP_001159392.1	P08697-1
	SERPINF2	NM_001165921.2		c.109A>C	p.Ser37Arg	missense	Exon 4 of 9	NP_001159393.1	P08697-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINF2	ENST00000453066.6	TSL:5 MANE Select	c.109A>C	p.Ser37Arg	missense	Exon 4 of 10	ENSP00000402286.2	P08697-1
	SERPINF2	ENST00000382061.5	TSL:1	c.109A>C	p.Ser37Arg	missense	Exon 4 of 10	ENSP00000371493.4	P08697-1
	SERPINF2	ENST00000883620.1		c.109A>C	p.Ser37Arg	missense	Exon 4 of 11	ENSP00000553679.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.0072	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	1.7
DANN	Benign	0.86
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.26
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.84	N
REVEL	Uncertain	0.36
Sift	Benign	0.058	T
Sift4G	Uncertain	0.043	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.094
gMVP		0.34

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-1648633;