Variant X-135158282-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001031705.3(CT55):c.454G>A(p.Glu152Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 112,142 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

CT55
NM_001031705.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12997809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CT55	NM_001031705.3 linkuse as main transcript	c.454G>A	p.Glu152Lys	missense_variant	4/6	ENST00000276241.11	NP_001026875.1	Q8WUE5-1
CT55	NM_017863.2 linkuse as main transcript	c.454G>A	p.Glu152Lys	missense_variant	4/5		NP_060333.1	Q8WUE5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CT55	ENST00000276241.11 linkuse as main transcript	c.454G>A	p.Glu152Lys	missense_variant	4/6	1	NM_001031705.3	ENSP00000276241.6		Q8WUE5-1
CT55	ENST00000344129.2 linkuse as main transcript	c.454G>A	p.Glu152Lys	missense_variant	4/5	1		ENSP00000343893.2		Q8WUE5-2

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112087

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34241

show subpopulations

Gnomad AFR

AF:

0.0000324

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000183

AC:

AN:

1091662

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

357268

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.0000284

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:

0.00

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34306

show subpopulations

Gnomad4 AFR

AF:

0.0000324

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:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.454G>A (p.E152K) alteration is located in exon 4 (coding exon 4) of the CT55 gene. This alteration results from a G to A substitution at nucleotide position 454, causing the glutamic acid (E) at amino acid position 152 to be replaced by a lysine (K). 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

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.056

T;.

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

1.0

N;N

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.038

Sift

Benign

0.18

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.0030

B;.

Vest4

0.23

MutPred

0.43

Gain of ubiquitination at E152 (P = 0.0219);Gain of ubiquitination at E152 (P = 0.0219);

MVP

0.043

MPC

0.21

ClinPred

0.11

GERP RS

1.3

Varity_R

0.11

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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