rs2071069

Positions:

• chr12-6869846-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000365.6(TPI1):​c.543+73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,543,372 control chromosomes in the GnomAD database, including 63,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7551 hom., cov: 32)
  • Exomes 𝑓: 0.28 (55651 hom.)
• Consequence: TPI1 NM_000365.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.115

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-6869846-G-A is Benign according to our data. Variant chr12-6869846-G-A is described in ClinVar as [Benign]. Clinvar id is 1267337.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPI1	NM_000365.6	c.543+73G>A		intron_variant		ENST00000396705.10
TPI1	NM_001159287.1	c.654+73G>A		intron_variant
TPI1	NM_001258026.2	c.297+73G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPI1	ENST00000396705.10	c.543+73G>A		intron_variant		1	NM_000365.6	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46979 AN: 151868 Hom.: 7540 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.279 AC: 388031 AN: 1391386 Hom.: 55651 Cov.: 23 AF XY: 0.282 AC XY: 195938 AN XY: 695960

Gnomad4 AFR exome AF: 0.413

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.309 AC: 47023 AN: 151986 Hom.: 7551 Cov.: 32 AF XY: 0.306 AC XY: 22743 AN XY: 74282

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.327

Alfa AF: 0.286 Hom.: 1243

Bravo AF: 0.316

Asia WGS AF: 0.316 AC: 1098 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071069; hg19: chr12-6979010; COSMIC: COSV51290051; COSMIC: COSV51290051;