rs1320821

chr7-144770627-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.44-4676C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,838 control chromosomes in the GnomAD database, including 3,039 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 0.19 (3039 hom., cov: 32)
• Consequence: TPK1 NM_022445.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPK1	NM_022445.4	c.44-4676C>T		intron_variant		ENST00000360057.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPK1	ENST00000360057.7	c.44-4676C>T		intron_variant		1	NM_022445.4	P1
TPK1	ENST00000378098.8	c.44-4676C>T		intron_variant, NMD_transcript_variant		1
TPK1	ENST00000378099.7	c.44-4676C>T		intron_variant		3
TPK1	ENST00000552881.1	c.44-4676C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28870 AN: 151718 Hom.: 3044 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.190 AC: 28866 AN: 151838 Hom.: 3039 Cov.: 32 AF XY: 0.190 AC XY: 14097 AN XY: 74206

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.246

Alfa AF: 0.210 Hom.: 1502

Bravo AF: 0.186

Asia WGS AF: 0.191 AC: 663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.19
Dann	Benign	0.58

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: rs1320821; hg19: chr7-144467720;