rs1800201

Variant names:

• chr12-6867521-G-A
• rs1800201
• ENST00000229270.8:c.66G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-6867521-G-A
• chr12-6867521-G-C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.76
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TPI1	NM_001159287.1	c.66G>A	p.Pro22Pro	synonymous_variant	Exon 1 of 7		NP_001152759.1
TPI1	NM_000365.6	c.-46G>A		upstream_gene_variant		ENST00000396705.10	NP_000356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPI1	ENST00000229270.8	c.66G>A	p.Pro22Pro	synonymous_variant	Exon 1 of 7	1		ENSP00000229270.4
TPI1	ENST00000613953.4	c.66G>A	p.Pro22Pro	synonymous_variant	Exon 1 of 7	1		ENSP00000484435.1
TPI1	ENST00000396705.10	c.-46G>A		upstream_gene_variant		1	NM_000365.6	ENSP00000379933.4

Frequencies

GnomAD3 genomes AF: 0.0323 AC: 4918 AN: 152146 Hom.: 242 Cov.: 34

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

GnomAD2 exomes AF: 0.00844 AC: 1830 AN: 216926 AF XY: 0.00713

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 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.: 34 AF XY: 0.00581 AC XY: 4167 AN XY: 717010

African (AFR) AF: 0.118 AC: 3910 AN: 33050

American (AMR) AF: 0.00773 AC: 323 AN: 41766

Ashkenazi Jewish (ASJ) AF: 0.00334 AC: 86 AN: 25762

East Asian (EAS) AF: 0.000179 AC: 7 AN: 39044

South Asian (SAS) AF: 0.00156 AC: 132 AN: 84416

European-Finnish (FIN) AF: 0.000469 AC: 24 AN: 51138

Middle Eastern (MID) AF: 0.0228 AC: 130 AN: 5704

European-Non Finnish (NFE) AF: 0.00324 AC: 3580 AN: 1103484

Other (OTH) AF: 0.0108 AC: 647 AN: 59668

GnomAD4 genome AF: 0.0324 AC: 4928 AN: 152260 Hom.: 243 Cov.: 34 AF XY: 0.0320 AC XY: 2383 AN XY: 74450

African (AFR) AF: 0.107 AC: 4444 AN: 41534

American (AMR) AF: 0.0136 AC: 208 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00290 AC: 197 AN: 68000

Other (OTH) AF: 0.0265 AC: 56 AN: 2112

Alfa AF: 0.0151 Hom.: 58

Bravo AF: 0.0356

Asia WGS AF: 0.00955 AC: 34 AN: 3470

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Triosephosphate isomerase deficiency Benign:2

Sep 13, 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: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		1.8
PromoterAI		-0.25	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1800201; hg19: chr12-6976685;