14-23558751-C-T

Variant summary

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

The NM_024328.6(THTPA):​c.604C>T​(p.Arg202Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,614,082 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 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

THTPA
NM_024328.6 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.409
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=0.27194947).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THTPANM_024328.6 linkuse as main transcriptc.604C>T p.Arg202Trp missense_variant 2/2 ENST00000288014.7 NP_077304.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
THTPAENST00000288014.7 linkuse as main transcriptc.604C>T p.Arg202Trp missense_variant 2/21 NM_024328.6 ENSP00000288014 P1Q9BU02-1
ZFHX2-AS1ENST00000553985.1 linkuse as main transcriptn.295C>T non_coding_transcript_exon_variant 3/32

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
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:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000875
AC:
22
AN:
251480
Hom.:
0
AF XY:
0.0000736
AC XY:
10
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
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:
0.000167
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000170
AC:
248
AN:
1461884
Hom.:
0
Cov.:
30
AF XY:
0.000177
AC XY:
129
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000210
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.000135
AC XY:
10
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000814
Hom.:
0
Bravo
AF:
0.000121
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.000218
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 GeneticsDec 13, 2023The c.604C>T (p.R202W) alteration is located in exon 2 (coding exon 2) of the THTPA gene. This alteration results from a C to T substitution at nucleotide position 604, causing the arginine (R) at amino acid position 202 to be replaced by a tryptophan (W). 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
0.13
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.53
D;D;.
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Benign
0.59
D
LIST_S2
Uncertain
0.87
.;D;D
M_CAP
Benign
0.068
D
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.63
T
MutationAssessor
Benign
1.7
L;L;.
MutationTaster
Benign
0.99
D;D;D;D;N
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-2.9
D;D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0040
D;D;D
Sift4G
Uncertain
0.041
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.38
MVP
0.62
MPC
0.12
ClinPred
0.34
T
GERP RS
2.8
Varity_R
0.49
gMVP
0.53

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: rs146552511; hg19: chr14-24027960; API