X-135158240-C-T

Variant names:

• chrX-135158240-C-T
• rs1569481620
• NM_001031705.3:c.496G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A166S) has been classified 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
• Publications: 0 publications found

Genes affected

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

CT55 Gene-Disease associations (from GenCC):

• spermatogenic failure, X-linked, 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031705.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CT55	NM_001031705.3	MANE Select	c.496G>A	p.Ala166Thr	missense	Exon 4 of 6	NP_001026875.1	Q8WUE5-1
	CT55	NM_017863.2		c.496G>A	p.Ala166Thr	missense	Exon 4 of 5	NP_060333.1	Q8WUE5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CT55	ENST00000276241.11	TSL:1 MANE Select	c.496G>A	p.Ala166Thr	missense	Exon 4 of 6	ENSP00000276241.6	Q8WUE5-1
	CT55	ENST00000344129.2	TSL:1	c.496G>A	p.Ala166Thr	missense	Exon 4 of 5	ENSP00000343893.2	Q8WUE5-2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00000546 AC: 1 AN: 183229 AF XY: 0.00

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 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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.98
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.081
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.51		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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1569481620; hg19: chrX-134292165;