rs2872817

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.872
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 HGVSp Effect #exon/exons MANE UniProt
TKTL1NM_012253.4 linkuse as main transcriptc.*380A>G 3_prime_UTR_variant 13/13 ENST00000369915.8
TKTL1NM_001145933.2 linkuse as main transcriptc.*380A>G 3_prime_UTR_variant 13/13
TKTL1NM_001145934.2 linkuse as main transcriptc.*380A>G 3_prime_UTR_variant 12/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TKTL1ENST00000369915.8 linkuse as main transcriptc.*380A>G 3_prime_UTR_variant 13/131 NM_012253.4 P1P51854-3
TKTL1ENST00000369912.2 linkuse as main transcriptc.*380A>G 3_prime_UTR_variant 12/121 P51854-4
TKTL1ENST00000710264.1 linkuse as main transcriptc.*691A>G 3_prime_UTR_variant, NMD_transcript_variant 13/13

Frequencies

GnomAD3 genomes
AF:
0.236
AC:
26335
AN:
111502
Hom.:
2387
Cov.:
23
AF XY:
0.237
AC XY:
7980
AN XY:
33738
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.:
0
AF XY:
0.295
AC XY:
867
AN XY:
2936
show subpopulations
Gnomad4 AFR exome
AF:
0.320
Gnomad4 AMR exome
AF:
0.233
Gnomad4 ASJ exome
AF:
0.188
Gnomad4 EAS exome
AF:
0.225
Gnomad4 SAS exome
AF:
0.611
Gnomad4 FIN exome
AF:
0.207
Gnomad4 NFE exome
AF:
0.188
Gnomad4 OTH exome
AF:
0.215
GnomAD4 genome
AF:
0.236
AC:
26358
AN:
111559
Hom.:
2389
Cov.:
23
AF XY:
0.236
AC XY:
7994
AN XY:
33805
show subpopulations
Gnomad4 AFR
AF:
0.287
Gnomad4 AMR
AF:
0.228
Gnomad4 ASJ
AF:
0.219
Gnomad4 EAS
AF:
0.264
Gnomad4 SAS
AF:
0.564
Gnomad4 FIN
AF:
0.200
Gnomad4 NFE
AF:
0.198
Gnomad4 OTH
AF:
0.257
Alfa
AF:
0.212
Hom.:
6206
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
DANN
Benign
0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2872817; hg19: chrX-153558418; API