Variant 19-47802355-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001397346.1(TPRX1):c.821A>T(p.Asn274Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 16)

Exomes 𝑓: 0.00010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TPRX1
NM_001397346.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.73

Variant links:

Genes affected

TPRX1 (HGNC:32174): (tetrapeptide repeat homeobox 1) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the TPRX homeobox gene family. [provided by RefSeq, Jul 2008]

TPRX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021311611).

BP6

Variant 19-47802355-T-A is Benign according to our data. Variant chr19-47802355-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2371836.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPRX1	NM_001397346.1 linkuse as main transcript	c.821A>T	p.Asn274Ile	missense_variant	3/3	ENST00000698655.1	NP_001384275.1
TPRX1	NM_198479.3 linkuse as main transcript	c.947A>T	p.Asn316Ile	missense_variant	4/4		NP_940881.3	Q8N7U7D2CFI5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TPRX1	ENST00000698655.1 linkuse as main transcript	c.821A>T	p.Asn274Ile	missense_variant	3/3		NM_001397346.1	ENSP00000513863.1	A0A8V8TMK4
TPRX1	ENST00000535759.2 linkuse as main transcript	c.947A>T	p.Asn316Ile	missense_variant	4/4	1		ENSP00000438832.1	D2CFI5
TPRX1	ENST00000322175.8 linkuse as main transcript	c.605-132A>T		intron_variant		1		ENSP00000513867.1	A0A8V8TM49

Frequencies

GnomAD3 genomes

AF:

0.00113

AC:

AN:

60402

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.00237

Gnomad FIN

AF:

0.000677

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000813

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000170

AC:

AN:

106016

Hom.:

AF XY:

0.000157

AC XY:

AN XY:

57242

show subpopulations

Gnomad AFR exome

AF:

0.000435

Gnomad AMR exome

AF:

0.000560

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000599

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000102

AC:

104

AN:

1016422

Hom.:

Cov.:

AF XY:

0.0000922

AC XY:

AN XY:

499050

show subpopulations

Gnomad4 AFR exome

AF:

0.00104

Gnomad4 AMR exome

AF:

0.000475

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000188

Gnomad4 SAS exome

AF:

0.000101

Gnomad4 FIN exome

AF:

0.0000630

Gnomad4 NFE exome

AF:

0.0000546

Gnomad4 OTH exome

AF:

0.000335

GnomAD4 genome

AF:

0.00126

AC:

AN:

60460

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

30012

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.00238

Gnomad4 FIN

AF:

0.000677

Gnomad4 NFE

AF:

0.000813

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00608

Hom.:

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.00156

AC:

ExAC

AF:

0.0000436

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.19

DANN

Benign

0.28

DEOGEN2

Benign

0.0054

T;T;.

Eigen

Benign

-2.6

Eigen_PC

Benign

-2.7

FATHMM_MKL

Benign

0.00021

LIST_S2

Benign

0.13

T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

1.8

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.22

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.11

MVP

0.36

MPC

0.074

ClinPred

0.012

GERP RS

-0.80

Varity_R

0.092

gMVP

0.12

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