Variant chr14-23557296-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024328.6(THTPA):c.539G>A(p.Ser180Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

THTPA
NM_024328.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.656

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]

THTPA links:

ZFHX2-AS1 (HGNC:52658): (ZFHX2 antisense RNA 1)

ZFHX2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05038473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THTPA	NM_024328.6 linkuse as main transcript	c.539G>A	p.Ser180Asn	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 linkuse as main transcript	c.539G>A	p.Ser180Asn	missense_variant	1/2	1	NM_024328.6	ENSP00000288014	P1	Q9BU02-1
ZFHX2-AS1	ENST00000553985.1 linkuse as main transcript	n.239-1399G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000859

AC:

AN:

232900

Hom.:

AF XY:

0.00000790

AC XY:

AN XY:

126642

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1441724

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 02, 2024

The c.539G>A (p.S180N) 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 539, causing the serine (S) at amino acid position 180 to be replaced by an asparagine (N). 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

0.092

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.047

T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.56

.;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

D;D;D;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.084

Sift

Benign

0.20

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.0010

B;B

Vest4

0.18

MutPred

0.49

Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);

MVP

0.25

MPC

0.016

ClinPred

0.019

GERP RS

1.9

Varity_R

0.080

gMVP

0.22

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over