Genetic Variant CT55:p.Ile161Phe (chrX-135158255-T-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001031705.3(CT55):c.481A>T(p.Ile161Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,208,043 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 67 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 0.000098 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.00019 ( 0 hom. 65 hem. )

Consequence

CT55
NM_001031705.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.463

Publications

0 publications found

Variant links:

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)

CT55 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08986628).

BS2

High Hemizygotes in GnomAd4 at 2 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>T	p.Ile161Phe	missense	Exon 4 of 6	NP_001026875.1	Q8WUE5-1
	CT55	NM_017863.2		c.481A>T	p.Ile161Phe	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>T	p.Ile161Phe	missense	Exon 4 of 6	ENSP00000276241.6	Q8WUE5-1
	CT55	ENST00000344129.2	TSL:1	c.481A>T	p.Ile161Phe	missense	Exon 4 of 5	ENSP00000343893.2	Q8WUE5-2

Frequencies

GnomAD3 genomes

AF:

0.0000981

AC:

AN:

112141

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000873

AC:

AN:

183283

AF XY:

0.0000590

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000188

AC:

206

AN:

1095902

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

AN XY:

361330

show subpopulations

African (AFR)

AF:

0.0000759

AC:

AN:

26356

American (AMR)

AF:

0.00

AC:

AN:

35191

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19358

East Asian (EAS)

AF:

0.00

AC:

AN:

30181

South Asian (SAS)

AF:

0.00

AC:

AN:

54052

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40507

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.000238

AC:

200

AN:

840111

Other (OTH)

AF:

0.0000652

AC:

AN:

46016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000981

AC:

AN:

112141

Hom.:

Cov.:

AF XY:

0.0000583

AC XY:

AN XY:

34283

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30820

American (AMR)

AF:

0.000189

AC:

AN:

10598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3579

South Asian (SAS)

AF:

0.00

AC:

AN:

2692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6109

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.000150

AC:

AN:

53256

Other (OTH)

AF:

0.00

AC:

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000475

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.98

CADD

Benign

5.7

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.022

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.20

M_CAP

Benign

0.0034

MetaRNN

Benign

0.090

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.46

PROVEAN

Benign

-0.68

REVEL

Benign

0.016

Sift

Benign

0.18

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.11

MVP

0.043

MPC

0.29

ClinPred

0.038

GERP RS

1.0

Varity_R

0.062

gMVP

0.052

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over