rs228582

Positions:

• chr7-144722784-G-A
• chr7-144722784-G-C

Variant summary

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

The NM_022445.4(TPK1):​c.116-39806C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,544 control chromosomes in the GnomAD database, including 31,228 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 0.63 (31228 hom., cov: 27)
• Consequence: TPK1 NM_022445.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

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 (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPK1	NM_022445.4	c.116-39806C>T		intron_variant		ENST00000360057.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPK1	ENST00000360057.7	c.116-39806C>T		intron_variant		1	NM_022445.4	P1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95098 AN: 151426 Hom.: 31183 Cov.: 27

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.628 AC: 95203 AN: 151544 Hom.: 31228 Cov.: 27 AF XY: 0.627 AC XY: 46389 AN XY: 73986

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.577

Alfa AF: 0.549 Hom.: 30429

Bravo AF: 0.645

Asia WGS AF: 0.499 AC: 1736 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	0.82
DANN	Benign	0.25

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: rs228582; hg19: chr7-144419877;