rs10849038

Variant names:

• chr12-4328213-T-C
• rs10849038
• NM_020375.3:c.33-3067T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020375.3(TIGAR):​c.33-3067T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,050 control chromosomes in the GnomAD database, including 57,337 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 0.87 (57337 hom., cov: 30)
• Consequence: TIGAR NM_020375.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 1 publications found

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]

ENSG00000285901 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIGAR	NM_020375.3	c.33-3067T>C		intron_variant	Intron 1 of 5	ENST00000179259.6	NP_065108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIGAR	ENST00000179259.6	c.33-3067T>C		intron_variant	Intron 1 of 5	1	NM_020375.3	ENSP00000179259.4
ENSG00000285901	ENST00000674624.1	n.721-21606T>C		intron_variant	Intron 4 of 9			ENSP00000501898.1

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131779 AN: 151932 Hom.: 57293 Cov.: 30

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.867 AC: 131880 AN: 152050 Hom.: 57337 Cov.: 30 AF XY: 0.868 AC XY: 64512 AN XY: 74314

African (AFR) AF: 0.815 AC: 33770 AN: 41446

American (AMR) AF: 0.894 AC: 13654 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3157 AN: 3468

East Asian (EAS) AF: 0.979 AC: 5063 AN: 5170

South Asian (SAS) AF: 0.895 AC: 4316 AN: 4820

European-Finnish (FIN) AF: 0.900 AC: 9505 AN: 10564

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.874 AC: 59450 AN: 67982

Other (OTH) AF: 0.873 AC: 1848 AN: 2116

Alfa AF: 0.873 Hom.: 111451

Bravo AF: 0.865

Asia WGS AF: 0.917 AC: 3190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.32
DANN	Benign	0.17
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs10849038; hg19: chr12-4437379;