12-6867536-C-T

Position:

chr12-6867536-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The ENST00000229270.8(TPI1):c.81C>T(p.Asp27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,607,992 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00077 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

TPI1
ENST00000229270.8 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.72

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 12-6867536-C-T is Benign according to our data. Variant chr12-6867536-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 883746.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.72 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000768 (117/152324) while in subpopulation AFR AF= 0.00248 (103/41576). AF 95% confidence interval is 0.00209. There are 0 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPI1	NM_000365.6 linkuse as main transcript	c.-31C>T		5_prime_UTR_variant	1/7	ENST00000396705.10	NP_000356.1
TPI1	NM_001159287.1 linkuse as main transcript	c.81C>T	p.Asp27=	synonymous_variant	1/7		NP_001152759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPI1	ENST00000229270.8 linkuse as main transcript	c.81C>T	p.Asp27=	synonymous_variant	1/7	1		ENSP00000229270		P60174-3
TPI1	ENST00000613953.4 linkuse as main transcript	c.81C>T	p.Asp27=	synonymous_variant	1/7	1		ENSP00000484435		P60174-3
TPI1	ENST00000396705.10 linkuse as main transcript	c.-31C>T		5_prime_UTR_variant	1/7	1	NM_000365.6	ENSP00000379933	P1	P60174-1

Frequencies

GnomAD3 genomes

AF:

0.000762

AC:

116

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000268

AC:

AN:

235252

Hom.:

AF XY:

0.000256

AC XY:

AN XY:

129128

show subpopulations

Gnomad AFR exome

AF:

0.00308

Gnomad AMR exome

AF:

0.000120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000572

Gnomad SAS exome

AF:

0.000370

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000476

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000115

AC:

168

AN:

1455668

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

723860

show subpopulations

Gnomad4 AFR exome

AF:

0.00267

Gnomad4 AMR exome

AF:

0.000206

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.000269

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000768

AC:

117

AN:

152324

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000965

Hom.:

Bravo

AF:

0.000945

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Triosephosphate isomerase deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.4

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over