7-93887276-G-T

Variant names:

• chr7-93887276-G-T
• rs767746862
• NM_006528.4:c.616C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006528.4(TFPI2):​c.616C>A​(p.Arg206Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000823 in 1,458,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict 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)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: TFPI2 NM_006528.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054967523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFPI2	NM_006528.4	c.616C>A	p.Arg206Ser	missense_variant	Exon 4 of 5	ENST00000222543.11	NP_006519.1
TFPI2	NM_001271003.2	c.583C>A	p.Arg195Ser	missense_variant	Exon 4 of 5		NP_001257932.1
TFPI2	NM_001271004.2	c.540C>A	p.Asn180Lys	missense_variant	Exon 4 of 5		NP_001257933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFPI2	ENST00000222543.11	c.616C>A	p.Arg206Ser	missense_variant	Exon 4 of 5	1	NM_006528.4	ENSP00000222543.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000280 AC: 7 AN: 249694 Hom.: 0 AF XY: 0.0000297 AC XY: 4 AN XY: 134884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000823 AC: 12 AN: 1458716 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 725374

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.38
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.093
Sift	Pathogenic	0.0	D
MutPred		0.37		Gain of methylation at N101 (P = 0.0037);
MVP		0.27
ClinPred		0.092	T
GERP RS		-0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs767746862; hg19: chr7-93516588;