Variant chr12-6867505-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_001159287.1(TPI1):c.50T>A(p.Ile17Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 1,579,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

TPI1
NM_001159287.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a chain Triosephosphate isomerase (size 247) in uniprot entity TPIS_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_001159287.1

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27078366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPI1	NM_001159287.1 linkuse as main transcript	c.50T>A	p.Ile17Lys	missense_variant	1/7		NP_001152759.1	P60174-3
TPI1	NM_000365.6 linkuse as main transcript	c.-62T>A		upstream_gene_variant		ENST00000396705.10	NP_000356.1	P60174-1V9HWK1Q53HE2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TPI1	ENST00000229270.8 linkuse as main transcript	c.50T>A	p.Ile17Lys	missense_variant	1/7	1		ENSP00000229270.4	P60174-3
TPI1	ENST00000613953.4 linkuse as main transcript	c.50T>A	p.Ile17Lys	missense_variant	1/7	1		ENSP00000484435.1	P60174-3
TPI1	ENST00000396705.10 linkuse as main transcript	c.-62T>A		upstream_gene_variant		1	NM_000365.6	ENSP00000379933.4	P60174-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1427248

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707182

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151968

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.32

T;T

Eigen

Benign

0.080

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.52

.;T

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;N

PROVEAN

Benign

-0.11

N;.

REVEL

Benign

0.18

Sift

Benign

0.049

D;.

Sift4G

Benign

0.070

T;T

Vest4

0.33

MutPred

0.44

Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);

MVP

0.21

MPC

1.5

ClinPred

0.64

GERP RS

4.8

Varity_R

0.12

gMVP

0.42

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over