ENST00000229270.8:c.50T>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2

The ENST00000229270.8(TPI1):c.50T>G(p.Ile17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,579,330 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0038 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0029 ( 11 hom. )

Consequence

TPI1
ENST00000229270.8 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 2.12

Publications

15 publications found

Variant links:

Genes affected

TPI1 (HGNC:12009): (triosephosphate isomerase 1) This gene encodes an enzyme, consisting of two identical proteins, which catalyzes the isomerization of glyceraldehydes 3-phosphate (G3P) and dihydroxy-acetone phosphate (DHAP) in glycolysis and gluconeogenesis. Mutations in this gene are associated with triosephosphate isomerase deficiency. Pseudogenes have been identified on chromosomes 1, 4, 6 and 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

TPI1 Gene-Disease associations (from GenCC):

triosephosphate isomerase deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

TPI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 5 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: -0.22304 (below the threshold of 3.09). Trascript score misZ: 0.73719 (below the threshold of 3.09). GenCC associations: The gene is linked to triosephosphate isomerase deficiency.

BP4

Computational evidence support a benign effect (MetaRNN=0.008082598).

BP6

Variant 12-6867505-T-G is Benign according to our data. Variant chr12-6867505-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 811143.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Likely_benign=1}.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00377 (573/152082) while in subpopulation AFR AF = 0.00755 (313/41482). AF 95% confidence interval is 0.00686. There are 2 homozygotes in GnomAd4. There are 269 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPI1	NM_001159287.1 link	c.50T>G	p.Ile17Arg	missense_variant	Exon 1 of 7		NP_001152759.1	P60174-3
TPI1	NM_000365.6 link	c.-62T>G		upstream_gene_variant		ENST00000396705.10	NP_000356.1	P60174-1V9HWK1Q53HE2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TPI1	ENST00000229270.8 link	c.50T>G	p.Ile17Arg	missense_variant	Exon 1 of 7	1		ENSP00000229270.4	P60174-3
TPI1	ENST00000613953.4 link	c.50T>G	p.Ile17Arg	missense_variant	Exon 1 of 7	1		ENSP00000484435.1	P60174-3
TPI1	ENST00000396705.10 link	c.-62T>G		upstream_gene_variant		1	NM_000365.6	ENSP00000379933.4	P60174-1

Frequencies

GnomAD3 genomes

AF:

0.00379

AC:

576

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00754

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00307

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00210

AC:

405

AN:

193188

AF XY:

0.00218

show subpopulations

Gnomad AFR exome

AF:

0.00611

Gnomad AMR exome

AF:

0.00250

Gnomad ASJ exome

AF:

0.00236

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000389

Gnomad NFE exome

AF:

0.00233

Gnomad OTH exome

AF:

0.00461

GnomAD4 exome

AF:

0.00291

AC:

4160

AN:

1427248

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

2111

AN XY:

707182

show subpopulations

African (AFR)

AF:

0.00766

AC:

250

AN:

32620

American (AMR)

AF:

0.00278

AC:

108

AN:

38898

Ashkenazi Jewish (ASJ)

AF:

0.00334

AC:

AN:

25424

East Asian (EAS)

AF:

0.00

AC:

AN:

37986

South Asian (SAS)

AF:

0.00144

AC:

119

AN:

82662

European-Finnish (FIN)

AF:

0.000481

AC:

AN:

49946

Middle Eastern (MID)

AF:

0.0142

AC:

AN:

5580

European-Non Finnish (NFE)

AF:

0.00299

AC:

3270

AN:

1095004

Other (OTH)

AF:

0.00381

AC:

225

AN:

59128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

239

479

718

958

1197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00377

AC:

573

AN:

152082

Hom.:

Cov.:

AF XY:

0.00362

AC XY:

269

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00755

AC:

313

AN:

41482

American (AMR)

AF:

0.00301

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00104

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000284

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00262

AC:

178

AN:

67964

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00286

Hom.:

Bravo

AF:

0.00410

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.00219

AC:

262

Asia WGS

AF:

0.00260

AC:

AN:

3474

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:2Benign:1

Oct 18, 2022

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TPI1: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Triosephosphate isomerase deficiency

Uncertain:1

Jan 02, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.34

T;T

Eigen

Benign

0.082

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.51

.;T

MetaRNN

Benign

0.0081

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;N

PhyloP100

2.1

PROVEAN

Benign

-0.14

N;.

REVEL

Benign

0.21

Sift

Benign

0.16

T;.

Sift4G

Benign

0.11

T;T

Vest4

0.51

MVP

0.32

MPC

1.6

ClinPred

0.096

GERP RS

4.8

PromoterAI

-0.56

Under-expression

(source)

Varity_R

0.21

gMVP

0.37

Mutation Taster

=97/3

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

ENST00000229270.8:c.50T>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over