NM_000934.4:c.78C>T

Variant names:

• chr17-1745189-C-T
• rs764369234
• NM_000934.4:c.78C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000934.4(SERPINF2):​c.78C>T​(p.Ser26Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,567,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000060 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: SERPINF2 NM_000934.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -3.43
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 17-1745189-C-T is Benign according to our data. Variant chr17-1745189-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 728494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.43 with no splicing effect.

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.78C>T	p.Ser26Ser	synonymous	Exon 3 of 10	NP_000925.2	P08697-1
	SERPINF2	NM_001165920.1		c.78C>T	p.Ser26Ser	synonymous	Exon 3 of 10	NP_001159392.1	P08697-1
	SERPINF2	NM_001165921.2		c.78C>T	p.Ser26Ser	synonymous	Exon 3 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.78C>T	p.Ser26Ser	synonymous	Exon 3 of 10	ENSP00000402286.2	P08697-1
	SERPINF2	ENST00000382061.5	TSL:1	c.78C>T	p.Ser26Ser	synonymous	Exon 3 of 10	ENSP00000371493.4	P08697-1
	SERPINF2	ENST00000883620.1		c.78C>T	p.Ser26Ser	synonymous	Exon 3 of 11	ENSP00000553679.1

Frequencies

GnomAD3 genomes AF: 0.0000597 AC: 9 AN: 150874 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000490

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

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: 0.0000884

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000733 AC: 13 AN: 177436 AF XY: 0.0000738

Gnomad AFR exome AF: 0.0000974

Gnomad AMR exome AF: 0.000115

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000616

Gnomad NFE exome AF: 0.0000818

Gnomad OTH exome AF: 0.000209

GnomAD4 exome AF: 0.0000466 AC: 66 AN: 1416940 Hom.: 0 Cov.: 46 AF XY: 0.0000485 AC XY: 34 AN XY: 700904

African (AFR) AF: 0.0000928 AC: 3 AN: 32312

American (AMR) AF: 0.000107 AC: 4 AN: 37228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25338

East Asian (EAS) AF: 0.0000270 AC: 1 AN: 36992

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81696

European-Finnish (FIN) AF: 0.0000201 AC: 1 AN: 49802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.0000441 AC: 48 AN: 1089174

Other (OTH) AF: 0.000136 AC: 8 AN: 58744

GnomAD4 genome AF: 0.0000596 AC: 9 AN: 150984 Hom.: 0 Cov.: 30 AF XY: 0.0000543 AC XY: 4 AN XY: 73700

African (AFR) AF: 0.0000488 AC: 2 AN: 40956

American (AMR) AF: 0.0000662 AC: 1 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000884 AC: 6 AN: 67864

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000300 Hom.: 0

Bravo AF: 0.0000982

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SERPINF2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.8
DANN	Benign	0.52
PhyloP100		-3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs764369234; hg19: chr17-1648483;