X-54923415-A-C

Position:

• chrX-54923415-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039705.3(TRO):​c.883A>C​(p.Ile295Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 24)
• Consequence: TRO NM_001039705.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.322

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]

ACMG classification

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=0.042029113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRO	NM_001039705.3	c.883A>C	p.Ile295Leu	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	c.883A>C	p.Ile295Leu	missense_variant	3/13	1	NM_001039705.3	ENSP00000173898	A2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.883A>C (p.I295L) alteration is located in exon 3 (coding exon 2) of the TRO gene. This alteration results from a A to C substitution at nucleotide position 883, causing the isoleucine (I) at amino acid position 295 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	0.11
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.58
DEOGEN2	Benign	0.061	T;.;.
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.50	T;.;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.042	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.77	N;N;N
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.45	N;N;N
REVEL	Benign	0.011
Sift	Benign	0.99	T;T;T
Sift4G	Benign	0.74	T;T;T
Polyphen		0.0020	B;.;.
Vest4		0.13
MutPred		0.20		Loss of catalytic residue at P297 (P = 0.0298);Loss of catalytic residue at P297 (P = 0.0298);Loss of catalytic residue at P297 (P = 0.0298);
MVP		0.092
MPC		0.15
ClinPred		0.029	T
GERP RS		-2.9
Varity_R		0.073
gMVP		0.023

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-54949848;