Variant X-54924677-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001271183.2(TRO):c.-59A>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000744 in 1,210,108 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 4 hem. )

Consequence

TRO
NM_001271183.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.40

Variant links:

Genes affected

TRO (HGNC:12326): (trophinin) This gene encodes a membrane protein that mediates cell adhesion between trophoblastic cells and the epithelial cells of the endometrium. The encoded protein participates in cell signalling during embryo implantation, and may also be involved in cancer formation. This gene is located near several other closely related genes on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

TRO links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15847406).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRO	NM_001039705.3 link	c.1349A>T	p.Lys450Met	missense_variant	5/13	ENST00000173898.12	NP_001034794.1	Q12816-1Q9BX91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRO	ENST00000173898.12 link	c.1349A>T	p.Lys450Met	missense_variant	5/13	1	NM_001039705.3	ENSP00000173898.7		Q12816-1

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112105

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34279

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:

0.000280

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:

0.0000441

AC:

AN:

181568

Hom.:

AF XY:

0.0000593

AC XY:

AN XY:

67416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000590

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:

0.00000729

AC:

AN:

1097947

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363307

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000232

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112161

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34345

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000248

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

Mar 22, 2023

The c.1349A>T (p.K450M) alteration is located in exon 5 (coding exon 4) of the TRO gene. This alteration results from a A to T substitution at nucleotide position 1349, causing the lysine (K) at amino acid position 450 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

Pathogenic

0.62

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;.;.;.;.;.

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

T;.;T;T;T;T;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.16

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.28

N;N;.;N;.;.;.

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-4.1

D;D;.;D;D;D;D

REVEL

Benign

0.17

Sift

Benign

0.062

T;T;.;T;T;T;T

Sift4G

Uncertain

0.0080

D;D;T;D;T;D;D

Polyphen

1.0

D;.;.;.;.;.;.

Vest4

0.48

MutPred

0.43

Loss of MoRF binding (P = 0.0465);Loss of MoRF binding (P = 0.0465);.;Loss of MoRF binding (P = 0.0465);.;.;.;

MVP

0.16

MPC

0.20

ClinPred

0.42

GERP RS

1.9

Varity_R

0.25

gMVP

0.51

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