12-4331308-A-G

Position:

• chr12-4331308-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020375.3(TIGAR):​c.61A>G​(p.Ile21Val) variant causes a missense 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TIGAR NM_020375.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.111602366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIGAR	NM_020375.3	c.61A>G	p.Ile21Val	missense_variant	2/6	ENST00000179259.6	NP_065108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIGAR	ENST00000179259.6	c.61A>G	p.Ile21Val	missense_variant	2/6	1	NM_020375.3	ENSP00000179259.4
ENSG00000285901	ENST00000674624.1	n.721-18511A>G		intron_variant				ENSP00000501898.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.61A>G (p.I21V) alteration is located in exon 2 (coding exon 2) of the TIGAR gene. This alteration results from a A to G substitution at nucleotide position 61, causing the isoleucine (I) at amino acid position 21 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.24	N
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.14
Sift	Benign	0.036	D
Sift4G	Benign	0.30	T
Polyphen		0.0080	B
Vest4		0.22
MutPred		0.51		Gain of catalytic residue at I22 (P = 0.0059);
MVP		0.12
MPC		0.42
ClinPred		0.10	T
GERP RS		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.070
gMVP		0.091

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-4440474;