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. Variant got 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. 13/21 in silico tools predict 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: 33)
• Consequence: TKT NM_001064.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TKT	NM_001064.4	c.898A>G	p.Asn300Asp	missense_variant	Exon 7 of 14	ENST00000462138.6	NP_001055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TKT	ENST00000462138.6	c.898A>G	p.Asn300Asp	missense_variant	Exon 7 of 14	1	NM_001064.4	ENSP00000417773.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.10
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.64	.;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.8	N;N;N;.
REVEL	Benign	0.17
Sift	Benign	0.60	T;T;T;.
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.37
MutPred		0.55		Gain of disorder (P = 0.0498);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs143676012; hg19: chr3-53265417;