Variant X-54922594-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000173898.12(TRO):c.62C>T(p.Pro21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,206,812 control chromosomes in the GnomAD database, including 1 homozygotes. There are 75 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P21R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., 36 hem., cov: 22)

Exomes 𝑓: 0.00013 ( 1 hom. 39 hem. )

Consequence

TRO
ENST00000173898.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

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:

TRO (HGNC:):

TRO links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0086737275).

BS2

High Hemizygotes in GnomAd4 at 36 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRO	NM_001039705.3 linkuse as main transcript	c.62C>T	p.Pro21Leu	missense_variant	3/13	ENST00000173898.12	NP_001034794.1	Q12816-1Q9BX91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRO	ENST00000173898.12 linkuse as main transcript	c.62C>T	p.Pro21Leu	missense_variant	3/13	1	NM_001039705.3	ENSP00000173898.7		Q12816-1

Frequencies

GnomAD3 genomes

AF:

0.000979

AC:

109

AN:

111379

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

33597

show subpopulations

Gnomad AFR

AF:

0.00347

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000379

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000256

AC:

AN:

175461

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

62275

show subpopulations

Gnomad AFR exome

AF:

0.00351

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000113

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000127

AC:

139

AN:

1095384

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

361176

show subpopulations

Gnomad4 AFR exome

AF:

0.00368

Gnomad4 AMR exome

AF:

0.0000286

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000168

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000274

Gnomad4 OTH exome

AF:

0.000196

GnomAD4 genome

AF:

0.000978

AC:

109

AN:

111428

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

33656

show subpopulations

Gnomad4 AFR

AF:

0.00346

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000380

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000523

Hom.:

Bravo

AF:

0.00140

ESP6500AA

AF:

0.00402

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000190

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

Dec 08, 2023

The c.62C>T (p.P21L) alteration is located in exon 3 (coding exon 2) of the TRO gene. This alteration results from a C to T substitution at nucleotide position 62, causing the proline (P) at amino acid position 21 to be replaced by a leucine (L). 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

0.096

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.11

.;T;.;.;.;.

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.82

.;T;.;T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0087

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N;N;N;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.5

N;N;N;N;N;N

REVEL

Benign

0.053

Sift

Uncertain

0.018

D;T;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.0020

.;B;.;.;.;.

Vest4

0.25, 0.26

MVP

0.48

MPC

0.15

ClinPred

0.028

GERP RS

-1.0

Varity_R

0.074

gMVP

0.081

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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