Variant 19-2807451-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003249.5(THOP1):c.896C>T(p.Ala299Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000402 in 1,590,298 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

THOP1
NM_003249.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

Variant links:

Genes affected

THOP1 (HGNC:11793): (thimet oligopeptidase 1) The protein encoded by this gene is a kininase that uses zinc as a cofactor. The encoded oligopeptidase cleaves cytosolic peptides, making them unavailable for display on antigen-presenting cells. This protein also cleaves neuropeptides under 20 aa in length and can degrade beta-amyloid precursor protein to amyloidogenic peptides. [provided by RefSeq, Nov 2015]

THOP1 links:

THOP1 (HGNC:):

THOP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THOP1	NM_003249.5 linkuse as main transcript	c.896C>T	p.Ala299Val	missense_variant	8/13	ENST00000307741.11	NP_003240.1	P52888-1
THOP1	XM_011528228.3 linkuse as main transcript	c.269C>T	p.Ala90Val	missense_variant	5/10		XP_011526530.1
THOP1	XM_047439299.1 linkuse as main transcript	c.896C>T	p.Ala299Val	missense_variant	8/10		XP_047295255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
THOP1	ENST00000307741.11 linkuse as main transcript	c.896C>T	p.Ala299Val	missense_variant	8/13	1	NM_003249.5	ENSP00000304467.5	P52888-1
THOP1	ENST00000586677.5 linkuse as main transcript	c.533C>T	p.Ala178Val	missense_variant	5/10	2		ENSP00000467226.1	K7EP46
THOP1	ENST00000589087.5 linkuse as main transcript	n.1046C>T		non_coding_transcript_exon_variant	2/6	2
THOP1	ENST00000591149.5 linkuse as main transcript	n.78C>T		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152222

Hom.:

Cov.:

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000463

AC:

AN:

237340

Hom.:

AF XY:

0.0000309

AC XY:

AN XY:

129592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000340

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000944

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000355

AC:

AN:

1438076

Hom.:

Cov.:

AF XY:

0.0000365

AC XY:

AN XY:

711828

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.0000394

Gnomad4 EAS exome

AF:

0.0000510

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.0000195

Gnomad4 NFE exome

AF:

0.0000392

Gnomad4 OTH exome

AF:

0.0000339

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74366

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000245

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000166

AC:

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

Jul 12, 2022

The c.896C>T (p.A299V) alteration is located in exon 8 (coding exon 8) of the THOP1 gene. This alteration results from a C to T substitution at nucleotide position 896, causing the alanine (A) at amino acid position 299 to be replaced by a valine (V). 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

0.22

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.8

D;.

REVEL

Benign

0.18

Sift

Benign

0.17

T;.

Sift4G

Benign

0.30

T;T

Polyphen

1.0

D;.

Vest4

0.60

MVP

0.51

MPC

0.87

ClinPred

0.69

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.57

gMVP

0.37

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