14-23557007-G-A

Variant summary

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

The NM_024328.6(THTPA):​c.250G>A​(p.Ala84Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

THTPA
NM_024328.6 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78
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=0.106107146).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THTPANM_024328.6 linkuse as main transcriptc.250G>A p.Ala84Thr 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.250G>A p.Ala84Thr missense_variant 1/21 NM_024328.6 ENSP00000288014 P1Q9BU02-1
ZFHX2-AS1ENST00000553985.1 linkuse as main transcriptn.239-1688G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152198
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251466
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000568
AC:
83
AN:
1461894
Hom.:
0
Cov.:
30
AF XY:
0.0000536
AC XY:
39
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000728
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152316
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74478
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:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsMar 07, 2024The c.250G>A (p.A84T) alteration is located in exon 1 (coding exon 1) of the THTPA gene. This alteration results from a G to A substitution at nucleotide position 250, causing the alanine (A) at amino acid position 84 to be replaced by a threonine (T). 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
Benign
0.080
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
19
DANN
Benign
0.92
DEOGEN2
Benign
0.054
T;T;T;.;.;.
Eigen
Benign
-0.061
Eigen_PC
Benign
0.015
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.77
.;T;T;.;T;T
M_CAP
Benign
0.0070
T
MetaRNN
Benign
0.11
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.8
M;M;.;M;.;M
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.79
N;N;N;N;N;N
REVEL
Benign
0.057
Sift
Benign
0.42
T;T;T;D;T;D
Sift4G
Benign
0.59
T;T;T;T;T;T
Polyphen
0.55
P;P;.;.;.;.
Vest4
0.13
MVP
0.39
MPC
0.021
ClinPred
0.37
T
GERP RS
4.5
Varity_R
0.15
gMVP
0.43

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: rs561860798; hg19: chr14-24026216; API