rs12230555

Positions:

• chr12-4309618-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000635110.1(TIGAR):​c.-146+862T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 145,876 control chromosomes in the GnomAD database, including 18,393 homozygotes. 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: 𝑓 0.47 (18393 hom., cov: 29)
• Consequence: TIGAR ENST00000635110.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

Genes affected

TIGAR (HGNC:1185): (TP53 induced glycolysis regulatory phosphatase) This gene is regulated as part of the p53 tumor suppressor pathway and encodes a protein with sequence similarity to the bisphosphate domain of the glycolytic enzyme that degrades fructose-2,6-bisphosphate. The protein functions by blocking glycolysis and directing the pathway into the pentose phosphate shunt. Expression of this protein also protects cells from DNA damaging reactive oxygen species and provides some protection from DNA damage-induced apoptosis. The 12p13.32 region that includes this gene is paralogous to the 11q13.3 region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIGAR	ENST00000635110.1	c.-146+862T>C		intron_variant		5		ENSP00000488928

Frequencies

GnomAD3 genomes AF: 0.468 AC: 68238 AN: 145770 Hom.: 18376 Cov.: 29

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.468 AC: 68262 AN: 145876 Hom.: 18393 Cov.: 29 AF XY: 0.471 AC XY: 33570 AN XY: 71294

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.503

Alfa AF: 0.568 Hom.: 29009

Bravo AF: 0.452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.61
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12230555; hg19: chr12-4418784;