chr14-23556789-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_024328.6(THTPA):āc.32A>Gā(p.Lys11Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,414 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
THTPA
NM_024328.6 missense
NM_024328.6 missense
Scores
3
11
5
Clinical Significance
Conservation
PhyloP100: 3.93
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
In a mutagenesis_site Mildly decreases enzyme activity. (size 0) in uniprot entity THTPA_HUMAN
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
THTPA | NM_024328.6 | c.32A>G | p.Lys11Arg | missense_variant | 1/2 | ENST00000288014.7 | NP_077304.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
THTPA | ENST00000288014.7 | c.32A>G | p.Lys11Arg | missense_variant | 1/2 | 1 | NM_024328.6 | ENSP00000288014 | P1 | |
ZFHX2-AS1 | ENST00000553985.1 | n.239-1906A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249180Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134762
GnomAD3 exomes
AF:
AC:
1
AN:
249180
Hom.:
AF XY:
AC XY:
1
AN XY:
134762
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461414Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726964
GnomAD4 exome
AF:
AC:
1
AN:
1461414
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
726964
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.32A>G (p.K11R) alteration is located in exon 1 (coding exon 1) of the THTPA gene. This alteration results from a A to G substitution at nucleotide position 32, causing the lysine (K) at amino acid position 11 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;D;T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T;.;T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;H;.;H;.;H
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
B;B;.;.;.;.
Vest4
MutPred
Loss of methylation at K11 (P = 0.0029);Loss of methylation at K11 (P = 0.0029);Loss of methylation at K11 (P = 0.0029);Loss of methylation at K11 (P = 0.0029);Loss of methylation at K11 (P = 0.0029);Loss of methylation at K11 (P = 0.0029);
MVP
MPC
0.045
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at