rs2071069

Variant names:

• chr12-6869846-G-A
• rs2071069
• NM_000365.6:c.543+73G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-6869846-G-A
• chr12-6869846-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.115
• Publications: 10 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 -20 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 VariationId is 1267337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
TPI1	NM_000365.6	c.543+73G>A		intron_variant	Intron 5 of 6	ENST00000396705.10	NP_000356.1
TPI1	NM_001159287.1	c.654+73G>A		intron_variant	Intron 5 of 6		NP_001152759.1
TPI1	NM_001258026.2	c.297+73G>A		intron_variant	Intron 5 of 6		NP_001244955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPI1	ENST00000396705.10	c.543+73G>A		intron_variant	Intron 5 of 6	1	NM_000365.6	ENSP00000379933.4

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

African (AFR) AF: 0.413 AC: 13253 AN: 32068

American (AMR) AF: 0.220 AC: 9740 AN: 44186

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 6592 AN: 25678

East Asian (EAS) AF: 0.197 AC: 7723 AN: 39298

South Asian (SAS) AF: 0.341 AC: 28909 AN: 84762

European-Finnish (FIN) AF: 0.240 AC: 12606 AN: 52436

Middle Eastern (MID) AF: 0.373 AC: 2102 AN: 5630

European-Non Finnish (NFE) AF: 0.276 AC: 290115 AN: 1049314

Other (OTH) AF: 0.293 AC: 16991 AN: 58014

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

African (AFR) AF: 0.404 AC: 16720 AN: 41426

American (AMR) AF: 0.277 AC: 4224 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1113 AN: 5154

South Asian (SAS) AF: 0.334 AC: 1606 AN: 4814

European-Finnish (FIN) AF: 0.233 AC: 2470 AN: 10580

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.278 AC: 18866 AN: 67952

Other (OTH) AF: 0.327 AC: 691 AN: 2112

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.43
PhyloP100		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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