chr7-93886854-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_006528.4(TFPI2):c.674G>A(p.Ser225Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,551,428 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S225R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 1 hom. )

Consequence

TFPI2
NM_006528.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.54

Publications

1 publications found

Variant links:

Genes affected

TFPI2 (HGNC:11761): (tissue factor pathway inhibitor 2) This gene encodes a member of the Kunitz-type serine proteinase inhibitor family. The protein can inhibit a variety of serine proteases including factor VIIa/tissue factor, factor Xa, plasmin, trypsin, chymotryspin and plasma kallikrein. This gene has been identified as a tumor suppressor gene in several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

TFPI2 links:

GNGT1 (HGNC:4411): (G protein subunit gamma transducin 1) This gene encodes the gamma subunit of transducin, a guanine nucleotide-binding protein (G protein) that is found in rod outer segments. Transducin, also known as GMPase, mediates the activation of a cyclic GTP-specific (guanosine monophosphate) phosphodiesterase by rhodopsin. [provided by RefSeq, Jul 2016]

GNGT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032977253).

BP6

Variant 7-93886854-C-T is Benign according to our data. Variant chr7-93886854-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3806325.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006528.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TFPI2	NM_006528.4	MANE Select	c.674G>A	p.Ser225Asn	missense	Exon 5 of 5	NP_006519.1	P48307-1
TFPI2	NM_001271003.2		c.641G>A	p.Ser214Asn	missense	Exon 5 of 5	NP_001257932.1	P48307-2
TFPI2	NM_001271004.2		c.*37G>A		3_prime_UTR	Exon 5 of 5	NP_001257933.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TFPI2	ENST00000222543.11	TSL:1 MANE Select	c.674G>A	p.Ser225Asn	missense	Exon 5 of 5	ENSP00000222543.5	P48307-1
TFPI2	ENST00000650573.1		c.692G>A	p.Ser231Asn	missense	Exon 5 of 5	ENSP00000497131.1	A0A3B3IS67
TFPI2	ENST00000898459.1		c.503G>A	p.Ser168Asn	missense	Exon 4 of 4	ENSP00000568518.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152144

Hom.:

Cov.:

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000678

AC:

AN:

191880

AF XY:

0.000113

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000931

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.0000314

AC:

AN:

1399284

Hom.:

Cov.:

AF XY:

0.0000460

AC XY:

AN XY:

695732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29100

American (AMR)

AF:

0.00

AC:

AN:

28530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24362

East Asian (EAS)

AF:

0.00

AC:

AN:

36594

South Asian (SAS)

AF:

0.0000795

AC:

AN:

75462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47534

Middle Eastern (MID)

AF:

0.000534

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.0000302

AC:

AN:

1094154

Other (OTH)

AF:

0.0000345

AC:

AN:

57934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000172

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.0040

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.078

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.28

M_CAP

Benign

0.0061

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.76

PhyloP100

-1.5

PrimateAI

Benign

0.34

PROVEAN

Benign

0.17

REVEL

Benign

0.0050

Sift

Benign

0.48

Sift4G

Benign

0.39

Polyphen

0.0

Vest4

0.055

MutPred

0.30

Loss of phosphorylation at S225 (P = 0.0013)

MVP

0.30

MPC

0.12

ClinPred

0.026

GERP RS

-4.1

Varity_R

0.029

gMVP

0.18

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over