Variant 12-6867524-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001159287.1(TPI1):c.69A>G(p.Arg23Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 1,599,278 control chromosomes in the GnomAD database, including 4,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.095 ( 1764 hom., cov: 34)

Exomes 𝑓: 0.023 ( 3168 hom. )

Consequence

TPI1
NM_001159287.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.87

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 12-6867524-A-G is Benign according to our data. Variant chr12-6867524-A-G is described in ClinVar as [Benign]. Clinvar id is 369027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.87 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPI1	NM_001159287.1 link	c.69A>G	p.Arg23Arg	synonymous_variant	Exon 1 of 7		NP_001152759.1	P60174-3
TPI1	NM_000365.6 link	c.-43A>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.69A>G	p.Arg23Arg	synonymous_variant	Exon 1 of 7	1		ENSP00000229270.4	P60174-3
TPI1	ENST00000613953.4 link	c.69A>G	p.Arg23Arg	synonymous_variant	Exon 1 of 7	1		ENSP00000484435.1	P60174-3
TPI1	ENST00000396705.10 link	c.-43A>G		upstream_gene_variant		1	NM_000365.6	ENSP00000379933.4	P60174-1

Frequencies

GnomAD3 genomes

AF:

0.0944

AC:

14357

AN:

152040

Hom.:

1741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.0126

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.00468

Gnomad OTH

AF:

0.0927

GnomAD3 exomes

AF:

0.0586

AC:

12998

AN:

221854

Hom.:

1330

AF XY:

0.0479

AC XY:

5840

AN XY:

121878

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.268

Gnomad SAS exome

AF:

0.00945

Gnomad FIN exome

AF:

0.000401

Gnomad NFE exome

AF:

0.00443

Gnomad OTH exome

AF:

0.0359

GnomAD4 exome

AF:

0.0233

AC:

33782

AN:

1447126

Hom.:

3168

Cov.:

AF XY:

0.0217

AC XY:

15611

AN XY:

718882

show subpopulations

Gnomad4 AFR exome

AF:

0.277

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.0236

Gnomad4 EAS exome

AF:

0.260

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.000467

Gnomad4 NFE exome

AF:

0.00443

Gnomad4 OTH exome

AF:

0.0400

GnomAD4 genome

AF:

0.0948

AC:

14424

AN:

152152

Hom.:

1764

Cov.:

AF XY:

0.0944

AC XY:

7022

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.261

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.0205

Gnomad4 EAS

AF:

0.256

Gnomad4 SAS

AF:

0.0124

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00468

Gnomad4 OTH

AF:

0.0936

Alfa

AF:

0.0425

Hom.:

306

Bravo

AF:

0.111

Asia WGS

AF:

0.106

AC:

367

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Triosephosphate isomerase deficiency

Benign:2

Nov 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27884173, 8571957, 10910933, 10575546) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.85

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