Genetic Variant CT47B1:p.Gly188Arg (chrX-120875109-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.562G>C(p.Gly188Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000414 in 1,208,636 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G188S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 9 hem., cov: 22)

Exomes 𝑓: 0.000022 ( 0 hom. 8 hem. )

Consequence

CT47B1
NM_001145718.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.761

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=0.07889384).

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CT47B1	NM_001145718.3 link	c.562G>C	p.Gly188Arg	missense_variant	Exon 1 of 3	ENST00000371311.5	NP_001139190.1	P0C2W7
CT47B1	XM_017029734.3 link	c.562G>C	p.Gly188Arg	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.562G>C	p.Gly188Arg	missense_variant	Exon 1 of 3	5	NM_001145718.3	ENSP00000360360.3		P0C2W7

Frequencies

GnomAD3 genomes

AF:

0.000231

AC:

AN:

112499

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

AN XY:

34667

show subpopulations

Gnomad AFR

AF:

0.000840

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

GnomAD3 exomes

AF:

0.0000607

AC:

AN:

181292

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

67084

show subpopulations

Gnomad AFR exome

AF:

0.000631

Gnomad AMR exome

AF:

0.0000366

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:

0.000223

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1096137

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

362229

show subpopulations

Gnomad4 AFR exome

AF:

0.000683

Gnomad4 AMR exome

AF:

0.0000569

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:

0.00

Gnomad4 OTH exome

AF:

0.0000653

GnomAD4 genome

AF:

0.000231

AC:

AN:

112499

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

AN XY:

34667

show subpopulations

Gnomad4 AFR

AF:

0.000840

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

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000249

ExAC

AF:

0.0000746

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.562G>C (p.G188R) 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 562, causing the glycine (G) at amino acid position 188 to be replaced by an arginine (R). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.4

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.63

M_CAP

Benign

0.0023

MetaRNN

Benign

0.079

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.034

Sift

Uncertain

0.0040

Sift4G

Benign

0.18

Polyphen

1.0

Vest4

0.023

MVP

0.085

MPC

0.024

ClinPred

0.24

GERP RS

2.0

Varity_R

0.22

gMVP

0.018

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