14-23556882-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000288014.7(THTPA):​c.125C>T​(p.Thr42Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000446 in 1,613,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

THTPA
ENST00000288014.7 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.77
Variant links:
Genes affected
THTPA (HGNC:18987): (thiamine triphosphatase) This gene encodes an enzyme which catalyzes the biosynthesis of thiamine disphophate (vitamin B1) by hydrolysis of thiamine triphosphate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]
ZFHX2-AS1 (HGNC:52658): (ZFHX2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18031755).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THTPANM_024328.6 linkuse as main transcriptc.125C>T p.Thr42Ile missense_variant 1/2 ENST00000288014.7 NP_077304.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
THTPAENST00000288014.7 linkuse as main transcriptc.125C>T p.Thr42Ile missense_variant 1/21 NM_024328.6 ENSP00000288014 P1Q9BU02-1
ZFHX2-AS1ENST00000553985.1 linkuse as main transcriptn.239-1813C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000882
AC:
22
AN:
249350
Hom.:
0
AF XY:
0.0000964
AC XY:
13
AN XY:
134864
show subpopulations
Gnomad AFR exome
AF:
0.0000621
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00170
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000267
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000452
AC:
66
AN:
1461320
Hom.:
0
Cov.:
30
AF XY:
0.0000454
AC XY:
33
AN XY:
726892
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00168
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000127
Hom.:
0
Bravo
AF:
0.0000529
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000577
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 04, 2022The c.125C>T (p.T42I) alteration is located in exon 1 (coding exon 1) of the THTPA gene. This alteration results from a C to T substitution at nucleotide position 125, causing the threonine (T) at amino acid position 42 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Benign
-0.030
T
BayesDel_noAF
Benign
-0.10
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.53
D;D;T;.;.;.
Eigen
Benign
0.018
Eigen_PC
Benign
0.050
FATHMM_MKL
Benign
0.67
D
LIST_S2
Benign
0.83
.;T;T;.;T;T
M_CAP
Uncertain
0.085
D
MetaRNN
Benign
0.18
T;T;T;T;T;T
MetaSVM
Benign
-0.64
T
MutationAssessor
Pathogenic
3.6
H;H;.;H;.;H
MutationTaster
Benign
0.97
D;D;D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-3.8
D;D;D;D;D;D
REVEL
Benign
0.26
Sift
Uncertain
0.0020
D;D;D;D;D;D
Sift4G
Uncertain
0.0080
D;D;D;D;D;D
Polyphen
0.66
P;P;.;.;.;.
Vest4
0.79
MVP
0.56
MPC
0.13
ClinPred
0.67
D
GERP RS
4.0
Varity_R
0.52
gMVP
0.79

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: rs368793622; hg19: chr14-24026091; API