Variant X-54922980-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000173898.12(TRO):c.448G>A(p.Ala150Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,240 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

TRO
ENST00000173898.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.147

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:

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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=0.034146726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRO	NM_001039705.3 linkuse as main transcript	c.448G>A	p.Ala150Thr	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.448G>A	p.Ala150Thr	missense_variant	3/13	1	NM_001039705.3	ENSP00000173898.7		Q12816-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363594

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

Cov.:

Bravo

AF:

0.0000113

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 29, 2023

The c.448G>A (p.A150T) alteration is located in exon 3 (coding exon 2) of the TRO gene. This alteration results from a G to A substitution at nucleotide position 448, causing the alanine (A) at amino acid position 150 to be replaced by a threonine (T). 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

0.073

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.0

DANN

Benign

0.53

DEOGEN2

Benign

0.024

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

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.65

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

M_CAP

Benign

0.0064

MetaRNN

Benign

0.034

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;.;.;L;L;L;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.85

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.041

Sift

Benign

0.90

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

Sift4G

Benign

0.32

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

Polyphen

0.0040

.;.;.;B;.;.;.;.;.;.

Vest4

0.076, 0.040

MutPred

0.082

.;Gain of glycosylation at A150 (P = 0.0353);.;Gain of glycosylation at A150 (P = 0.0353);Gain of glycosylation at A150 (P = 0.0353);Gain of glycosylation at A150 (P = 0.0353);Gain of glycosylation at A150 (P = 0.0353);.;Gain of glycosylation at A150 (P = 0.0353);.;

MVP

0.30

MPC

0.15

ClinPred

0.017

GERP RS

-1.3

Varity_R

0.036

gMVP

0.071

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