rs1800200

chr12-6867524-A-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The ENST00000229270.8(TPI1):c.69A>G(p.Arg23=) 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 ENST00000229270.8 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.87

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]

ACMG classification

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/exons	MANE	UniProt
TPI1	NM_001159287.1	c.69A>G	p.Arg23=	synonymous_variant	1/7
TPI1	NM_000365.6			upstream_gene_variant		ENST00000396705.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPI1	ENST00000229270.8	c.69A>G	p.Arg23=	synonymous_variant	1/7	1
TPI1	ENST00000613953.4	c.69A>G	p.Arg23=	synonymous_variant	1/7	1
TPI1	ENST00000396705.10			upstream_gene_variant		1	NM_000365.6	P1

Frequencies

GnomAD3 genomes AF: 0.0944 AC: 14357 AN: 152040 Hom.: 1741 Cov.: 34

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

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.: 34 AF XY: 0.0217 AC XY: 15611 AN XY: 718882

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.: 34 AF XY: 0.0944 AC XY: 7022 AN XY: 74402

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Triosephosphate isomerase deficiency Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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	17
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1800200; hg19: chr12-6976688;