chr7-144722784-G-A

Variant summary

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

The NM_022445.4(TPK1):​c.116-39806C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,544 control chromosomes in the GnomAD database, including 31,228 homozygotes. 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 0.63 ( 31228 hom., cov: 27)

Consequence

TPK1
NM_022445.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.100

Publications

8 publications found
Variant links:
Genes affected
TPK1 (HGNC:17358): (thiamin pyrophosphokinase 1) The protein encoded by this gene functions as a homodimer and catalyzes the conversion of thiamine to thiamine pyrophosphate, a cofactor for some enzymes of the glycolytic and energy production pathways. Defects in this gene are a cause of thiamine metabolism dysfunction syndrome-5. [provided by RefSeq, Apr 2017]
TPK1 Gene-Disease associations (from GenCC):
  • childhood encephalopathy due to thiamine pyrophosphokinase deficiency
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
  • Leigh syndrome
    Inheritance: AR Classification: MODERATE Submitted by: ClinGen

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=-0.99).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TPK1NM_022445.4 linkc.116-39806C>T intron_variant Intron 3 of 8 ENST00000360057.7 NP_071890.2 Q9H3S4-1A0A090N8Y0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TPK1ENST00000360057.7 linkc.116-39806C>T intron_variant Intron 3 of 8 1 NM_022445.4 ENSP00000353165.3 Q9H3S4-1

Frequencies

GnomAD3 genomes
AF:
0.628
AC:
95098
AN:
151426
Hom.:
31183
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.833
Gnomad AMI
AF:
0.834
Gnomad AMR
AF:
0.623
Gnomad ASJ
AF:
0.551
Gnomad EAS
AF:
0.491
Gnomad SAS
AF:
0.528
Gnomad FIN
AF:
0.551
Gnomad MID
AF:
0.487
Gnomad NFE
AF:
0.537
Gnomad OTH
AF:
0.584
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.628
AC:
95203
AN:
151544
Hom.:
31228
Cov.:
27
AF XY:
0.627
AC XY:
46389
AN XY:
73986
show subpopulations
African (AFR)
AF:
0.833
AC:
34429
AN:
41330
American (AMR)
AF:
0.623
AC:
9491
AN:
15242
Ashkenazi Jewish (ASJ)
AF:
0.551
AC:
1909
AN:
3462
East Asian (EAS)
AF:
0.492
AC:
2510
AN:
5102
South Asian (SAS)
AF:
0.529
AC:
2529
AN:
4782
European-Finnish (FIN)
AF:
0.551
AC:
5763
AN:
10456
Middle Eastern (MID)
AF:
0.503
AC:
148
AN:
294
European-Non Finnish (NFE)
AF:
0.537
AC:
36454
AN:
67868
Other (OTH)
AF:
0.577
AC:
1211
AN:
2098
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1608
3217
4825
6434
8042
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
760
1520
2280
3040
3800
<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:
0.559
Hom.:
43188
Bravo
AF:
0.645
Asia WGS
AF:
0.499
AC:
1736
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
0.82
DANN
Benign
0.25
PhyloP100
0.10
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

Publications

Other links and lift over

dbSNP: rs228582; hg19: chr7-144419877; API