rs59999573

Variant names:

• chr7-93890078-C-G
• rs59999573
• NM_006528.4:c.271+59G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-93890078-C-G
• chr7-93890078-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006528.4(TFPI2):​c.271+59G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,341,198 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: TFPI2 NM_006528.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFPI2	NM_006528.4	c.271+59G>C		intron_variant	Intron 2 of 4	ENST00000222543.11	NP_006519.1
TFPI2	NM_001271003.2	c.238+59G>C		intron_variant	Intron 2 of 4		NP_001257932.1
TFPI2	NM_001271004.2	c.271+59G>C		intron_variant	Intron 2 of 4		NP_001257933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFPI2	ENST00000222543.11	c.271+59G>C		intron_variant	Intron 2 of 4	1	NM_006528.4	ENSP00000222543.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1341198 Hom.: 0 Cov.: 26 AF XY: 0.00000152 AC XY: 1 AN XY: 656168

African (AFR) AF: 0.00 AC: 0 AN: 29610

American (AMR) AF: 0.00 AC: 0 AN: 31308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20314

East Asian (EAS) AF: 0.00 AC: 0 AN: 36206

South Asian (SAS) AF: 0.00 AC: 0 AN: 68972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5214

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1045172

Other (OTH) AF: 0.00 AC: 0 AN: 54870

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.36
DANN	Benign	0.51
PhyloP100		-1.9
PromoterAI		-0.087	Neutral

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: rs59999573; hg19: chr7-93519390;