rs143676012

Variant names:

• chr3-53231401-T-C
• rs143676012
• NM_001064.4:c.898A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-53231401-T-C
• chr3-53231401-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001064.4(TKT):​c.898A>G​(p.Asn300Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N300H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TKT NM_001064.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.25
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21236542).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TKT	NM_001064.4	MANE Select	c.898A>G	p.Asn300Asp	missense	Exon 7 of 14	NP_001055.1
	TKT	NM_001258028.2		c.922A>G	p.Asn308Asp	missense	Exon 8 of 15	NP_001244957.1
	TKT	NM_001135055.3		c.898A>G	p.Asn300Asp	missense	Exon 7 of 15	NP_001128527.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TKT	ENST00000462138.6	TSL:1 MANE Select	c.898A>G	p.Asn300Asp	missense	Exon 7 of 14	ENSP00000417773.1
	TKT	ENST00000423525.6	TSL:1	c.898A>G	p.Asn300Asp	missense	Exon 7 of 15	ENSP00000405455.2
	TKT	ENST00000423516.5	TSL:2	c.922A>G	p.Asn308Asp	missense	Exon 8 of 15	ENSP00000391481.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Benign	0.80
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.10
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		6.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.17
Sift	Benign	0.60	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.37
MutPred		0.55		Gain of disorder (P = 0.0498)
MVP		0.44
MPC		0.42
ClinPred		0.48	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.63
gMVP		0.62
Mutation Taster		=19/81	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs143676012; hg19: chr3-53265417;