chr3-53248287-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001064.4(TKT):​c.108-6045T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,110 control chromosomes in the GnomAD database, including 46,187 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 0.76 (46187 hom., 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 Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TKT	NM_001064.4	c.108-6045T>C		intron_variant	Intron 1 of 13	ENST00000462138.6	NP_001055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TKT	ENST00000462138.6	c.108-6045T>C		intron_variant	Intron 1 of 13	1	NM_001064.4	ENSP00000417773.1

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114825 AN: 151992 Hom.: 46165 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.755 AC: 114896 AN: 152110 Hom.: 46187 Cov.: 32 AF XY: 0.758 AC XY: 56372 AN XY: 74336

African (AFR) AF: 0.457 AC: 18932 AN: 41446

American (AMR) AF: 0.864 AC: 13207 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3121 AN: 3472

East Asian (EAS) AF: 0.955 AC: 4940 AN: 5174

South Asian (SAS) AF: 0.850 AC: 4101 AN: 4822

European-Finnish (FIN) AF: 0.804 AC: 8516 AN: 10588

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59379 AN: 68006

Other (OTH) AF: 0.780 AC: 1648 AN: 2114

Alfa AF: 0.839 Hom.: 203898

Bravo AF: 0.748

Asia WGS AF: 0.878 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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;