7-144714388-C-T

Position:

• chr7-144714388-C-T

Variant summary

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

The NM_022445.4(TPK1):​c.116-31410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,864 control chromosomes in the GnomAD database, including 6,976 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 0.27 (6976 hom., cov: 32)
• Consequence: TPK1 NM_022445.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPK1	NM_022445.4	c.116-31410G>A		intron_variant		ENST00000360057.7	NP_071890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPK1	ENST00000360057.7	c.116-31410G>A		intron_variant		1	NM_022445.4	ENSP00000353165	P1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41468 AN: 151746 Hom.: 6977 Cov.: 32

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.273 AC: 41470 AN: 151864 Hom.: 6976 Cov.: 32 AF XY: 0.279 AC XY: 20736 AN XY: 74228

Gnomad4 AFR AF: 0.0719

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.259

Alfa AF: 0.299 Hom.: 3777

Bravo AF: 0.268

Asia WGS AF: 0.316 AC: 1093 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.3
DANN	Benign	0.69

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: rs228581; hg19: chr7-144411481;