rs782578713

Variant names:

• chr3-53225856-C-G
• rs782578713
• NM_001064.4:c.1772G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-53225856-C-G
• chr3-53225856-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001064.4(TKT):​c.1772G>C​(p.Arg591Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R591Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TKT NM_001064.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29739195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TKT	NM_001064.4	c.1772G>C	p.Arg591Pro	missense_variant	Exon 14 of 14	ENST00000462138.6	NP_001055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TKT	ENST00000462138.6	c.1772G>C	p.Arg591Pro	missense_variant	Exon 14 of 14	1	NM_001064.4	ENSP00000417773.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461844 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.0044	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Benign	0.86
DEOGEN2	Uncertain	0.73	D;D;.;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.66
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.95	.;D;D;D
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.3	M;M;.;.
PhyloP100		1.9
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.9	N;N;N;.
REVEL	Benign	0.28
Sift	Benign	0.13	T;T;T;.
Sift4G	Benign	0.16	T;T;T;T
Polyphen		0.24	B;B;.;.
Vest4		0.21
MVP		0.71
MPC		0.78
ClinPred		0.25	T
GERP RS		1.8
Varity_R		0.70
gMVP		0.88
Mutation Taster		=56/44	polymorphism

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: rs782578713; hg19: chr3-53259872;