3-53225980-G-A

Variant names:

• chr3-53225980-G-A
• rs3816767
• NM_001064.4:c.1697-49C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001064.4(TKT):​c.1697-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,558,256 control chromosomes in the GnomAD database, including 143,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11880 hom., cov: 32)
  • Exomes 𝑓: 0.43 (132001 hom.)
• Consequence: TKT NM_001064.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.119
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-53225980-G-A is Benign according to our data. Variant chr3-53225980-G-A is described in ClinVar as [Benign]. Clinvar id is 1342213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TKT	NM_001064.4	c.1697-49C>T		intron_variant	Intron 13 of 13	ENST00000462138.6	NP_001055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TKT	ENST00000462138.6	c.1697-49C>T		intron_variant	Intron 13 of 13	1	NM_001064.4	ENSP00000417773.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58065 AN: 152020 Hom.: 11866 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.432

GnomAD2 exomes AF: 0.442 AC: 96863 AN: 219080 AF XY: 0.450

Gnomad AFR exome AF: 0.233

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.525

Gnomad EAS exome AF: 0.600

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.438

Gnomad OTH exome AF: 0.464

GnomAD4 exome AF: 0.430 AC: 604622 AN: 1406114 Hom.: 132001 Cov.: 26 AF XY: 0.434 AC XY: 302067 AN XY: 695240

African (AFR) AF: 0.234 AC: 7544 AN: 32206

American (AMR) AF: 0.410 AC: 16685 AN: 40726

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 12313 AN: 23830

East Asian (EAS) AF: 0.560 AC: 21599 AN: 38544

South Asian (SAS) AF: 0.537 AC: 42879 AN: 79810

European-Finnish (FIN) AF: 0.379 AC: 19594 AN: 51646

Middle Eastern (MID) AF: 0.498 AC: 1943 AN: 3904

European-Non Finnish (NFE) AF: 0.424 AC: 456428 AN: 1077730

Other (OTH) AF: 0.444 AC: 25637 AN: 57718

GnomAD4 genome AF: 0.382 AC: 58107 AN: 152142 Hom.: 11880 Cov.: 32 AF XY: 0.386 AC XY: 28683 AN XY: 74376

African (AFR) AF: 0.238 AC: 9886 AN: 41506

American (AMR) AF: 0.429 AC: 6555 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1847 AN: 3472

East Asian (EAS) AF: 0.581 AC: 2999 AN: 5166

South Asian (SAS) AF: 0.547 AC: 2632 AN: 4814

European-Finnish (FIN) AF: 0.374 AC: 3954 AN: 10586

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28955 AN: 67986

Other (OTH) AF: 0.431 AC: 911 AN: 2112

Alfa AF: 0.411 Hom.: 33053

Bravo AF: 0.377

Asia WGS AF: 0.525 AC: 1826 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Transketolase deficiency Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.58
PhyloP100		0.12
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: rs3816767; hg19: chr3-53259996; COSMIC: COSV56247405; COSMIC: COSV56247405;