dbSNP rs2872817: TKTL1:c.*380A>G (chrX-154330068-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012253.4(TKTL1):c.*380A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 128,469 control chromosomes in the GnomAD database, including 2,732 homozygotes. There are 8,861 hemizygotes in GnomAD. 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 0.24 ( 2389 hom., 7994 hem., cov: 23)

Exomes 𝑓: 0.22 ( 343 hom. 867 hem. )

Consequence

TKTL1
NM_012253.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.872

Publications

8 publications found

Variant links:

Genes affected

TKTL1 (HGNC:11835): (transketolase like 1) The protein encoded by this gene is a transketolase that acts as a homodimer and catalyzes the conversion of sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to D-ribose 5-phosphate and D-xylulose 5-phosphate. This reaction links the pentose phosphate pathway with the glycolytic pathway. Variations in this gene may be the cause of Wernicke-Korsakoff syndrome. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

TKTL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TKTL1	NM_012253.4 link	c.*380A>G	3_prime_UTR_variant	Exon 13 of 13	ENST00000369915.8	NP_036385.3	P51854-3
TKTL1	NM_001145933.2 link	c.*380A>G	3_prime_UTR_variant	Exon 13 of 13		NP_001139405.1	B7Z7I0
TKTL1	NM_001145934.2 link	c.*380A>G	3_prime_UTR_variant	Exon 12 of 12		NP_001139406.1	P51854-4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TKTL1	ENST00000369915.8 link	c.*380A>G	3_prime_UTR_variant	Exon 13 of 13	1	NM_012253.4	ENSP00000358931.3	P51854-3
TKTL1	ENST00000369912.2 link	c.*380A>G	3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000358928.2	P51854-4
TKTL1	ENST00000710264.1 link	n.*691A>G	non_coding_transcript_exon_variant	Exon 13 of 13			ENSP00000518160.1
TKTL1	ENST00000710264.1 link	n.*691A>G	3_prime_UTR_variant	Exon 13 of 13			ENSP00000518160.1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

26335

AN:

111502

Hom.:

2387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.00873

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.247

GnomAD4 exome

AF:

0.221

AC:

3734

AN:

16910

Hom.:

343

Cov.:

AF XY:

0.295

AC XY:

867

AN XY:

2936

show subpopulations

African (AFR)

AF:

0.320

AC:

166

AN:

518

American (AMR)

AF:

0.233

AC:

244

AN:

1046

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

AN:

500

East Asian (EAS)

AF:

0.225

AC:

198

AN:

879

South Asian (SAS)

AF:

0.611

AC:

508

AN:

831

European-Finnish (FIN)

AF:

0.207

AC:

156

AN:

754

Middle Eastern (MID)

AF:

0.339

AC:

AN:

European-Non Finnish (NFE)

AF:

0.188

AC:

2142

AN:

11365

Other (OTH)

AF:

0.215

AC:

207

AN:

961

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

111

223

334

446

557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.236

AC:

26358

AN:

111559

Hom.:

2389

Cov.:

AF XY:

0.236

AC XY:

7994

AN XY:

33805

show subpopulations

African (AFR)

AF:

0.287

AC:

8786

AN:

30658

American (AMR)

AF:

0.228

AC:

2405

AN:

10560

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

578

AN:

2642

East Asian (EAS)

AF:

0.264

AC:

939

AN:

3554

South Asian (SAS)

AF:

0.564

AC:

1504

AN:

2669

European-Finnish (FIN)

AF:

0.200

AC:

1211

AN:

6058

Middle Eastern (MID)

AF:

0.205

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.198

AC:

10491

AN:

52984

Other (OTH)

AF:

0.257

AC:

393

AN:

1528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

702

1404

2106

2808

3510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.216

Hom.:

9063

Bravo

AF:

0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.048

(source)

DANN

Benign

0.21

PhyloP100

-0.87

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over