Genetic Variant CT55:p.Asp83Gly (chrX-135169625-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001031705.3(CT55):c.248A>G(p.Asp83Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,207,856 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. 2 hem. )

Consequence

CT55
NM_001031705.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

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

CT55 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CT55	NM_001031705.3 link	c.248A>G	p.Asp83Gly	missense_variant	Exon 2 of 6	ENST00000276241.11	NP_001026875.1	Q8WUE5-1
CT55	NM_017863.2 link	c.248A>G	p.Asp83Gly	missense_variant	Exon 2 of 5		NP_060333.1	Q8WUE5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CT55	ENST00000276241.11 link	c.248A>G	p.Asp83Gly	missense_variant	Exon 2 of 6	1	NM_001031705.3	ENSP00000276241.6		Q8WUE5-1
CT55	ENST00000344129.2 link	c.248A>G	p.Asp83Gly	missense_variant	Exon 2 of 5	1		ENSP00000343893.2		Q8WUE5-2

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112234

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34388

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000559

AC:

AN:

178905

Hom.:

AF XY:

0.00

AC XY:

AN XY:

63617

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1095622

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

361176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000167

Gnomad4 OTH exome

AF:

0.0000652

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112234

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34388

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000375

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.248A>G (p.D83G) alteration is located in exon 2 (coding exon 2) of the CT55 gene. This alteration results from a A to G substitution at nucleotide position 248, causing the aspartic acid (D) at amino acid position 83 to be replaced by a glycine (G). 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

0.099

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.14

T;.

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Benign

0.068

Sift

Uncertain

0.016

D;D

Sift4G

Uncertain

0.036

D;D

Polyphen

0.27

B;.

Vest4

0.11

MutPred

0.42

Loss of stability (P = 0.0335);Loss of stability (P = 0.0335);

MVP

0.068

MPC

0.26

ClinPred

0.29

GERP RS

1.1

Varity_R

0.24

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.47

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.47

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over