Variant X-54923539-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001039705.3(TRO):c.1007G>A(p.Arg336Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,188,773 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes 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: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000011 ( 0 hom. 5 hem. )

Consequence

TRO
NM_001039705.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.232

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02792269).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRO	NM_001039705.3 linkuse as main transcript	c.1007G>A	p.Arg336Gln	missense_variant	3/13	ENST00000173898.12	NP_001034794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRO	ENST00000173898.12 linkuse as main transcript	c.1007G>A	p.Arg336Gln	missense_variant	3/13	1	NM_001039705.3	ENSP00000173898	A2	Q12816-1

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112390

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34576

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:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000142

AC:

AN:

140594

Hom.:

AF XY:

0.00

AC XY:

AN XY:

43232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000429

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000913

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:

0.0000111

AC:

AN:

1076332

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

350354

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000312

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000341

Gnomad4 SAS exome

AF:

0.0000194

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000964

Gnomad4 OTH exome

AF:

0.0000221

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112441

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34637

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:

0.0000375

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000845

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

Feb 28, 2023

The c.1007G>A (p.R336Q) 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 1007, causing the arginine (R) at amino acid position 336 to be replaced by a glutamine (Q). 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

0.094

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-1.1

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.055

T;.;.

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.72

T;.;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.028

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.71

N;N;N

REVEL

Benign

0.012

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.64

T;T;T

Polyphen

0.028

B;.;.

Vest4

0.042

MutPred

0.29

Loss of methylation at R336 (P = 0.0548);Loss of methylation at R336 (P = 0.0548);Loss of methylation at R336 (P = 0.0548);

MVP

0.095

MPC

0.17

ClinPred

0.015

GERP RS

-0.96

Varity_R

0.052

gMVP

0.079

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