3-53248287-A-T

Variant names:

• chr3-53248287-A-T
• rs4687718
• NM_001064.4:c.108-6045T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001064.4(TKT):​c.108-6045T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TKT NM_001064.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 31 publications found

Genes affected

TKT (HGNC:11834): (transketolase) This gene encodes a thiamine-dependent enzyme which plays a role in the channeling of excess sugar phosphates to glycolysis in the pentose phosphate pathway. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2012]

TKT Gene-Disease associations (from GenCC):

• transketolase deficiency

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001064.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TKT	NM_001064.4	MANE Select	c.108-6045T>A		intron	N/A	NP_001055.1	P29401-1
	TKT	NM_001258028.2		c.108-6045T>A		intron	N/A	NP_001244957.1	P29401-2
	TKT	NM_001135055.3		c.108-6045T>A		intron	N/A	NP_001128527.1	P29401-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TKT	ENST00000462138.6	TSL:1 MANE Select	c.108-6045T>A		intron	N/A	ENSP00000417773.1	P29401-1
	TKT	ENST00000423525.6	TSL:1	c.108-6045T>A		intron	N/A	ENSP00000405455.2	P29401-1
	TKT	ENST00000472528.5	TSL:1	n.108-4665T>A		intron	N/A	ENSP00000417312.1	F8WAX4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		-0.19

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

Other links and lift over

dbSNP: rs4687718; hg19: chr3-53282303;