Genetic Variant CT55:p.Ala104Ser (chrX-135160525-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001031705.3(CT55):c.310G>T(p.Ala104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000344 in 1,192,722 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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: 22)

Exomes 𝑓: 0.000036 ( 0 hom. 11 hem. )

Consequence

CT55
NM_001031705.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.898

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011258483).

BS2

High Hemizygotes in GnomAdExome4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CT55	NM_001031705.3 link	c.310G>T	p.Ala104Ser	missense_variant	Exon 3 of 6	ENST00000276241.11	NP_001026875.1	Q8WUE5-1
CT55	NM_017863.2 link	c.310G>T	p.Ala104Ser	missense_variant	Exon 3 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.310G>T	p.Ala104Ser	missense_variant	Exon 3 of 6	1	NM_001031705.3	ENSP00000276241.6		Q8WUE5-1
CT55	ENST00000344129.2 link	c.310G>T	p.Ala104Ser	missense_variant	Exon 3 of 5	1		ENSP00000343893.2		Q8WUE5-2

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34108

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000195

AC:

AN:

163916

Hom.:

AF XY:

0.000189

AC XY:

AN XY:

52900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00142

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

AF:

0.0000361

AC:

AN:

1080810

Hom.:

Cov.:

AF XY:

0.0000313

AC XY:

AN XY:

351310

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00121

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:

0.00

Gnomad4 OTH exome

AF:

0.0000221

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34108

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ExAC

AF:

0.000214

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.310G>T (p.A104S) alteration is located in exon 3 (coding exon 3) of the CT55 gene. This alteration results from a G to T substitution at nucleotide position 310, causing the alanine (A) at amino acid position 104 to be replaced by a serine (S). 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

0.082

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.015

DANN

Benign

0.19

DEOGEN2

Benign

0.0030

T;.

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.26

T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

PROVEAN

Benign

0.72

N;N

REVEL

Benign

0.020

Sift

Benign

0.75

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.43

B;.

Vest4

0.057

MutPred

0.25

Gain of glycosylation at A104 (P = 0.0053);Gain of glycosylation at A104 (P = 0.0053);

MVP

0.043

MPC

0.17

ClinPred

0.029

GERP RS

-1.1

Varity_R

0.042

gMVP

0.053

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

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