12-6867524-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

12 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 -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

GnomAD2 exomes

AF:

0.0586

AC:

12998

AN:

221854

AF XY:

0.0479

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 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

African (AFR)

AF:

0.277

AC:

9184

AN:

33098

American (AMR)

AF:

0.127

AC:

5370

AN:

42200

Ashkenazi Jewish (ASJ)

AF:

0.0236

AC:

609

AN:

25820

East Asian (EAS)

AF:

0.260

AC:

10202

AN:

39194

South Asian (SAS)

AF:

0.0102

AC:

864

AN:

84738

European-Finnish (FIN)

AF:

0.000467

AC:

AN:

51408

Middle Eastern (MID)

AF:

0.0416

AC:

238

AN:

5720

European-Non Finnish (NFE)

AF:

0.00443

AC:

4898

AN:

1105142

Other (OTH)

AF:

0.0400

AC:

2393

AN:

59806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1532

3065

4597

6130

7662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0948

AC:

14424

AN:

152152

Hom.:

1764

Cov.:

AF XY:

0.0944

AC XY:

7022

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.261

AC:

10836

AN:

41492

American (AMR)

AF:

0.105

AC:

1607

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0205

AC:

AN:

3466

East Asian (EAS)

AF:

0.256

AC:

1319

AN:

5150

South Asian (SAS)

AF:

0.0124

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00468

AC:

318

AN:

67990

Other (OTH)

AF:

0.0936

AC:

197

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

582

1163

1745

2326

2908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0322

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

(source)

DANN

Benign

0.85

PhyloP100

2.9

PromoterAI

0.16

Neutral

(source)

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

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

Publications

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12-6867524-A-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