Genetic Variant CT47B1:p.Glu233Gln (chrX-120874974-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001145718.3(CT47B1):c.697G>C(p.Glu233Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000538 in 1,208,975 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes 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 0.000036 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000056 ( 0 hom. 17 hem. )

Consequence

CT47B1
NM_001145718.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.22

Variant links:

Genes affected

CT47B1 (HGNC:33293): (cancer/testis antigen family 47 member B1)

CT47B1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13370389).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CT47B1	NM_001145718.3 link	c.697G>C	p.Glu233Gln	missense_variant	Exon 1 of 3	ENST00000371311.5	NP_001139190.1	P0C2W7
CT47B1	XM_017029734.3 link	c.697G>C	p.Glu233Gln	missense_variant	Exon 1 of 3		XP_016885223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CT47B1	ENST00000371311.5 link	c.697G>C	p.Glu233Gln	missense_variant	Exon 1 of 3	5	NM_001145718.3	ENSP00000360360.3		P0C2W7

Frequencies

GnomAD3 genomes

AF:

0.0000355

AC:

AN:

112653

Hom.:

Cov.:

AF XY:

0.0000574

AC XY:

AN XY:

34825

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:

0.0000752

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

182615

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

67569

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:

0.0000860

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000556

AC:

AN:

1096322

Hom.:

Cov.:

AF XY:

0.0000469

AC XY:

AN XY:

362306

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:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000666

Gnomad4 OTH exome

AF:

0.0000870

GnomAD4 genome

AF:

0.0000355

AC:

AN:

112653

Hom.:

Cov.:

AF XY:

0.0000574

AC XY:

AN XY:

34825

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:

0.0000752

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000496

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.697G>C (p.E233Q) alteration is located in exon 1 (coding exon 1) of the CT47B1 gene. This alteration results from a G to C substitution at nucleotide position 697, causing the glutamic acid (E) at amino acid position 233 to be replaced by a glutamine (Q). 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

0.15

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.1

DANN

Benign

0.83

DEOGEN2

Benign

0.039

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.35

M_CAP

Benign

0.00098

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.4

REVEL

Benign

0.067

Sift

Uncertain

0.028

Sift4G

Benign

0.075

Polyphen

0.94

Vest4

0.051

MVP

0.014

MPC

0.0055

ClinPred

0.043

GERP RS

1.4

Varity_R

0.090

gMVP

0.021

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

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