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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012253.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TKTL1	NM_012253.4	MANE Select	c.*380A>G	3_prime_UTR	Exon 13 of 13	NP_036385.3	P51854-3
TKTL1	NM_001145933.2		c.*380A>G	3_prime_UTR	Exon 13 of 13	NP_001139405.1	B7Z7I0
TKTL1	NM_001145934.2		c.*380A>G	3_prime_UTR	Exon 12 of 12	NP_001139406.1	P51854-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TKTL1	ENST00000369915.8	TSL:1 MANE Select	c.*380A>G	3_prime_UTR	Exon 13 of 13	ENSP00000358931.3	P51854-3
TKTL1	ENST00000369912.2	TSL:1	c.*380A>G	3_prime_UTR	Exon 12 of 12	ENSP00000358928.2	P51854-4
TKTL1	ENST00000710264.1		n.*691A>G	non_coding_transcript_exon	Exon 13 of 13	ENSP00000518160.1	A0AA34QVR6

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 v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over