X-135158255-T-C

Variant names:

• chrX-135158255-T-C
• rs371245819
• NM_001031705.3:c.481A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001031705.3(CT55):​c.481A>G​(p.Ile161Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 1,095,904 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I161F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000064 (0 hom. 3 hem.)
• Consequence: CT55 NM_001031705.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09460729).
• BS2: High Hemizygotes in GnomAdExome4 at 3 Unknown gene

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.481A>G	p.Ile161Val	missense	Exon 4 of 6	NP_001026875.1	Q8WUE5-1
	CT55	NM_017863.2		c.481A>G	p.Ile161Val	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.481A>G	p.Ile161Val	missense	Exon 4 of 6	ENSP00000276241.6	Q8WUE5-1
	CT55	ENST00000344129.2	TSL:1	c.481A>G	p.Ile161Val	missense	Exon 4 of 5	ENSP00000343893.2	Q8WUE5-2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000639 AC: 7 AN: 1095904 Hom.: 0 Cov.: 27 AF XY: 0.00000830 AC XY: 3 AN XY: 361330

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26356

American (AMR) AF: 0.00 AC: 0 AN: 35191

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19358

East Asian (EAS) AF: 0.00 AC: 0 AN: 30181

South Asian (SAS) AF: 0.00 AC: 0 AN: 54052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40507

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00000833 AC: 7 AN: 840113

Other (OTH) AF: 0.00 AC: 0 AN: 46016

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0332287), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 22

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.74
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.46
PROVEAN	Benign	0.64	N
REVEL	Benign	0.019
Sift	Benign	0.13	T
Sift4G	Benign	0.56	T
Polyphen		0.028	B
Vest4		0.080
MutPred		0.26		Gain of catalytic residue at I161 (P = 0.0149)
MVP		0.043
MPC		0.16
ClinPred		0.057	T
GERP RS		1.0
Varity_R		0.042
gMVP		0.045
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: rs371245819; hg19: chrX-134292180;