NM_006528.4:c.375C>T

Variant names:

• chr7-93889120-G-A
• rs150637497
• NM_006528.4:c.375C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006528.4(TFPI2):​c.375C>T​(p.Phe125Phe) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TFPI2 NM_006528.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 6 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.066 with no splicing effect.

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.375C>T	p.Phe125Phe	synonymous	Exon 3 of 5	NP_006519.1	P48307-1
	TFPI2	NM_001271003.2		c.342C>T	p.Phe114Phe	synonymous	Exon 3 of 5	NP_001257932.1	P48307-2
	TFPI2	NM_001271004.2		c.375C>T	p.Phe125Phe	synonymous	Exon 3 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.375C>T	p.Phe125Phe	synonymous	Exon 3 of 5	ENSP00000222543.5	P48307-1
	TFPI2	ENST00000650573.1		c.375C>T	p.Phe125Phe	synonymous	Exon 3 of 5	ENSP00000497131.1	A0A3B3IS67
	TFPI2	ENST00000898459.1		c.375C>T	p.Phe125Phe	synonymous	Exon 3 of 4	ENSP00000568518.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.62
PhyloP100		-0.066

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

Other links and lift over

dbSNP: rs150637497; hg19: chr7-93518432; COSMIC: COSV104549156; COSMIC: COSV104549156;