Variant rs1800201 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BA1

The NM_001159287.1(TPI1):c.66G>A(p.Pro22Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00862 in 1,596,292 control chromosomes in the GnomAD database, including 486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 243 hom., cov: 34)

Exomes 𝑓: 0.0061 ( 243 hom. )

Consequence

TPI1
NM_001159287.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.76

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 Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.16).

BP6

Variant 12-6867521-G-A is Benign according to our data. Variant chr12-6867521-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 369026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPI1	NM_001159287.1 linkuse as main transcript	c.66G>A	p.Pro22Pro	synonymous_variant	1/7		NP_001152759.1	P60174-3
TPI1	NM_000365.6 linkuse as main transcript	c.-46G>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.66G>A	p.Pro22Pro	synonymous_variant	1/7	1		ENSP00000229270.4	P60174-3
TPI1	ENST00000613953.4 linkuse as main transcript	c.66G>A	p.Pro22Pro	synonymous_variant	1/7	1		ENSP00000484435.1	P60174-3
TPI1	ENST00000396705.10 linkuse as main transcript	c.-46G>A		upstream_gene_variant		1	NM_000365.6	ENSP00000379933.4	P60174-1

Frequencies

GnomAD3 genomes

AF:

0.0323

AC:

4918

AN:

152146

Hom.:

242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00290

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.00844

AC:

1830

AN:

216926

Hom.:

AF XY:

0.00713

AC XY:

848

AN XY:

118996

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.00701

Gnomad ASJ exome

AF:

0.00246

Gnomad EAS exome

AF:

0.000122

Gnomad SAS exome

AF:

0.00123

Gnomad FIN exome

AF:

0.000358

Gnomad NFE exome

AF:

0.00279

Gnomad OTH exome

AF:

0.00718

GnomAD4 exome

AF:

0.00612

AC:

8839

AN:

1444032

Hom.:

243

Cov.:

AF XY:

0.00581

AC XY:

4167

AN XY:

717010

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.00773

Gnomad4 ASJ exome

AF:

0.00334

Gnomad4 EAS exome

AF:

0.000179

Gnomad4 SAS exome

AF:

0.00156

Gnomad4 FIN exome

AF:

0.000469

Gnomad4 NFE exome

AF:

0.00324

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.0324

AC:

4928

AN:

152260

Hom.:

243

Cov.:

AF XY:

0.0320

AC XY:

2383

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.0136

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00290

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0140

Hom.:

Bravo

AF:

0.0356

Asia WGS

AF:

0.00955

AC:

AN:

3470

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Triosephosphate isomerase deficiency

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 31, 2023	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.97

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over