chr17-1745341-C-G

Variant names:

• chr17-1745341-C-G
• rs185025710
• NM_000934.4:c.111C>G

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.111C>G​(p.Ser37Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S37S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SERPINF2 NM_000934.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.06
• 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: Orphanet, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

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=0.1462915).

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.111C>G	p.Ser37Arg	missense	Exon 4 of 10	NP_000925.2	P08697-1
	SERPINF2	NM_001165920.1		c.111C>G	p.Ser37Arg	missense	Exon 4 of 10	NP_001159392.1	P08697-1
	SERPINF2	NM_001165921.2		c.111C>G	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.111C>G	p.Ser37Arg	missense	Exon 4 of 10	ENSP00000402286.2	P08697-1
	SERPINF2	ENST00000382061.5	TSL:1	c.111C>G	p.Ser37Arg	missense	Exon 4 of 10	ENSP00000371493.4	P08697-1
	SERPINF2	ENST00000883620.1		c.111C>G	p.Ser37Arg	missense	Exon 4 of 11	ENSP00000553679.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461018 Hom.: 0 Cov.: 43 AF XY: 0.00000138 AC XY: 1 AN XY: 726802

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111846

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 28

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	0.052
DANN	Benign	0.76
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.5	L
PhyloP100		-1.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.84	N
REVEL	Uncertain	0.41
Sift	Benign	0.058	T
Sift4G	Uncertain	0.043	D
Polyphen		0.61	P
Vest4		0.10
MutPred		0.25		Gain of solvent accessibility (P = 0.006)
MVP		0.49
MPC		0.52
ClinPred		0.16	T
GERP RS		-8.6
Varity_R		0.084
gMVP		0.34
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs185025710; hg19: chr17-1648635;