X-135158240-C-T

Position:

• chrX-135158240-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031705.3(CT55):​c.496G>A​(p.Ala166Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: CT55 NM_001031705.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.980

Genes affected

CT55 (HGNC:26047): (cancer/testis antigen 55)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23416829).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CT55	NM_001031705.3	c.496G>A	p.Ala166Thr	missense_variant	4/6	ENST00000276241.11	NP_001026875.1
CT55	NM_017863.2	c.496G>A	p.Ala166Thr	missense_variant	4/5		NP_060333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CT55	ENST00000276241.11	c.496G>A	p.Ala166Thr	missense_variant	4/6	1	NM_001031705.3	ENSP00000276241.6
CT55	ENST00000344129.2	c.496G>A	p.Ala166Thr	missense_variant	4/5	1		ENSP00000343893.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.00000546 AC: 1 AN: 183229 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67687

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

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 Cov.: 27

GnomAD4 genome Cov.: 22

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

May 20, 2024

The c.496G>A (p.A166T) alteration is located in exon 4 (coding exon 4) of the CT55 gene. This alteration results from a G to A substitution at nucleotide position 496, causing the alanine (A) at amino acid position 166 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	0.23
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	N;N
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.081
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.044	D;T
Polyphen		1.0	D;.
Vest4		0.40
MutPred		0.51		Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP		0.082
MPC		0.63
ClinPred		0.93	D
GERP RS		0.30
Varity_R		0.17
gMVP		0.12

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

Other links and lift over

dbSNP: rs1569481620; hg19: chrX-134292165;