rs1026266842

Variant names:

• chr7-93887327-T-C
• rs1026266842
• NM_006528.4:c.565A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-93887327-T-C
• chr7-93887327-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006528.4(TFPI2):​c.565A>G​(p.Thr189Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,748 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: TFPI2 NM_006528.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2183046).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPI2	NM_006528.4	MANE Select	c.565A>G	p.Thr189Ala	missense	Exon 4 of 5	NP_006519.1	P48307-1
	TFPI2	NM_001271003.2		c.532A>G	p.Thr178Ala	missense	Exon 4 of 5	NP_001257932.1	P48307-2
	TFPI2	NM_001271004.2		c.489A>G	p.Ile163Met	missense	Exon 4 of 5	NP_001257933.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPI2	ENST00000222543.11	TSL:1 MANE Select	c.565A>G	p.Thr189Ala	missense	Exon 4 of 5	ENSP00000222543.5	P48307-1
	TFPI2	ENST00000650573.1		c.583A>G	p.Thr195Ala	missense	Exon 4 of 5	ENSP00000497131.1	A0A3B3IS67
	TFPI2	ENST00000451238.1	TSL:2	c.252A>G	p.Ile84Met	missense	Exon 3 of 4	ENSP00000416370.1	H7C4A3

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

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: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251274 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461546 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727072

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.000157 AC: 7 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111820

Other (OTH) AF: 0.0000828 AC: 5 AN: 60372

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74362

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.00105 AC: 16 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00143 AC: 3 AN: 2092

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.000510

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	0.26
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.98
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.22	T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.69	T
PhyloP100		2.2
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.10
Sift	Benign	0.14	T
MutPred		0.29		Gain of disorder (P = 0.1)
MVP		0.65
ClinPred		0.42	T
GERP RS		1.5
Varity_R		0.12
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1026266842; hg19: chr7-93516639; COSMIC: COSV55992312; COSMIC: COSV55992312;