14-23556814-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024328.6(THTPA):​c.57G>T​(p.Glu19Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,520 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

THTPA
NM_024328.6 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26647532).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THTPANM_024328.6 linkuse as main transcriptc.57G>T p.Glu19Asp 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.57G>T p.Glu19Asp missense_variant 1/21 NM_024328.6 ENSP00000288014 P1Q9BU02-1
ZFHX2-AS1ENST00000553985.1 linkuse as main transcriptn.239-1881G>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152182
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
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
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461338
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726920
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
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
Bravo
AF:
0.00000378

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 GeneticsDec 21, 2021The c.57G>T (p.E19D) alteration is located in exon 1 (coding exon 1) of the THTPA gene. This alteration results from a G to T substitution at nucleotide position 57, causing the glutamic acid (E) at amino acid position 19 to be replaced by an aspartic acid (D). 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
0.45
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;T;T;.;.;.
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.76
.;T;T;.;T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.27
T;T;T;T;T;T
MetaSVM
Benign
-0.67
T
MutationAssessor
Uncertain
2.8
M;M;.;M;.;M
MutationTaster
Benign
0.96
D;D;D;D;D
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-2.0
N;N;N;N;N;N
REVEL
Benign
0.27
Sift
Benign
0.15
T;T;T;T;T;T
Sift4G
Benign
0.31
T;T;T;T;T;T
Polyphen
0.99
D;D;.;.;.;.
Vest4
0.42
MutPred
0.57
Loss of disorder (P = 0.103);Loss of disorder (P = 0.103);Loss of disorder (P = 0.103);Loss of disorder (P = 0.103);Loss of disorder (P = 0.103);Loss of disorder (P = 0.103);
MVP
0.51
MPC
0.027
ClinPred
0.53
D
GERP RS
4.0
Varity_R
0.32
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1324322390; hg19: chr14-24026023; API