rs969356

chr7-144476230-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022445.4(TPK1):c.614-22567C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,032 control chromosomes in the GnomAD database, including 23,968 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23968 hom., cov: 33)
• Consequence: TPK1 NM_022445.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPK1	NM_022445.4	c.614-22567C>T		intron_variant		ENST00000360057.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPK1	ENST00000360057.7	c.614-22567C>T		intron_variant		1	NM_022445.4	P1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83637 AN: 151914 Hom.: 23968 Cov.: 33

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.564

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.550 AC: 83657 AN: 152032 Hom.: 23968 Cov.: 33 AF XY: 0.538 AC XY: 39989 AN XY: 74312

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.558

Alfa AF: 0.616 Hom.: 58521

Bravo AF: 0.546

Asia WGS AF: 0.266 AC: 928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.94
Dann	Benign	0.67

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: rs969356; hg19: chr7-144173323;