Variant chr7-144453614-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_022445.4(TPK1):c.663C>T(p.Tyr221=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,613,876 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 9 hom. )

Consequence

TPK1
NM_022445.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.19

Variant links:

Genes affected

TPK1 (HGNC:17358): (thiamin pyrophosphokinase 1) The protein encoded by this gene functions as a homodimer and catalyzes the conversion of thiamine to thiamine pyrophosphate, a cofactor for some enzymes of the glycolytic and energy production pathways. Defects in this gene are a cause of thiamine metabolism dysfunction syndrome-5. [provided by RefSeq, Apr 2017]

TPK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 7-144453614-G-A is Benign according to our data. Variant chr7-144453614-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 137693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.19 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00239 (364/152266) while in subpopulation SAS AF= 0.00395 (19/4814). AF 95% confidence interval is 0.00351. There are 0 homozygotes in gnomad4. There are 177 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPK1	NM_022445.4 linkuse as main transcript	c.663C>T	p.Tyr221=	synonymous_variant	9/9	ENST00000360057.7	NP_071890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPK1	ENST00000360057.7 linkuse as main transcript	c.663C>T	p.Tyr221=	synonymous_variant	9/9	1	NM_022445.4	ENSP00000353165	P1	Q9H3S4-1

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

364

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00390

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00253

AC:

636

AN:

251394

Hom.:

AF XY:

0.00291

AC XY:

396

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00425

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00361

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00336

AC:

4913

AN:

1461610

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

2465

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00493

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.00368

Gnomad4 OTH exome

AF:

0.00376

GnomAD4 genome

AF:

0.00239

AC:

364

AN:

152266

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00395

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00390

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00320

Hom.:

Bravo

AF:

0.00221

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00365

EpiControl

AF:

0.00486

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 16, 2013

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

TPK1: BP4, BP7 -

Childhood encephalopathy due to thiamine pyrophosphokinase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.0

DANN

Benign

0.85

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