Variant 19-47802216-A-C 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_001397346.1(TPRX1):c.960T>G(p.Ile320Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000394 in 1,599,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

TPRX1
NM_001397346.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.631

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 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=0.015702873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPRX1	NM_001397346.1 linkuse as main transcript	c.960T>G	p.Ile320Met	missense_variant	3/3	ENST00000698655.1	NP_001384275.1
TPRX1	NM_198479.3 linkuse as main transcript	c.1086T>G	p.Ile362Met	missense_variant	4/4		NP_940881.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TPRX1	ENST00000698655.1 linkuse as main transcript	c.960T>G	p.Ile320Met	missense_variant	3/3		NM_001397346.1	ENSP00000513863	A2
TPRX1	ENST00000535759.2 linkuse as main transcript	c.1086T>G	p.Ile362Met	missense_variant	4/4	1		ENSP00000438832	A2
TPRX1	ENST00000322175.8 linkuse as main transcript	c.612T>G	p.Ile204Met	missense_variant	4/4	1		ENSP00000513867	P4

Frequencies

GnomAD3 genomes

AF:

0.000248

AC:

AN:

141160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000856

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000817

AC:

AN:

244674

Hom.:

AF XY:

0.0000677

AC XY:

AN XY:

133014

show subpopulations

Gnomad AFR exome

AF:

0.00112

Gnomad AMR exome

AF:

0.0000875

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1458476

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725520

show subpopulations

Gnomad4 AFR exome

AF:

0.000600

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000248

AC:

AN:

141298

Hom.:

Cov.:

AF XY:

0.000247

AC XY:

AN XY:

68836

show subpopulations

Gnomad4 AFR

AF:

0.000854

Gnomad4 AMR

AF:

0.000209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000302

Hom.:

Bravo

AF:

0.000310

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

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

Jan 08, 2024

The c.795T>G (p.I265M) alteration is located in exon 2 (coding exon 2) of the TPRX1 gene. This alteration results from a T to G substitution at nucleotide position 795, causing the isoleucine (I) at amino acid position 265 to be replaced by a methionine (M). 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

0.15

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.42

CADD

Benign

1.9

DANN

Benign

0.29

DEOGEN2

Benign

0.019

T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.24

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.077

T;T;T

Sift4G

Benign

0.072

T;T;T

Polyphen

0.44

B;.;.

Vest4

0.10

MVP

0.12

MPC

0.062

ClinPred

0.0071

GERP RS

-0.45

Varity_R

0.11

gMVP

0.062

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