Genetic Variant CT47B1:p.Gly298Arg (chrX-120873904-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001145718.3(CT47B1):c.892G>A(p.Gly298Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000874 in 1,075,815 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 56 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 1 hem., cov: 12)

Exomes 𝑓: 0.000087 ( 0 hom. 56 hem. )

Failed GnomAD Quality Control

Consequence

CT47B1
NM_001145718.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.241

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014114708).

BP6

Variant X-120873904-C-T is Benign according to our data. Variant chrX-120873904-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2363990.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAdExome4 at 56 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CT47B1	NM_001145718.3 link	c.892G>A	p.Gly298Arg	missense_variant	Exon 2 of 3	ENST00000371311.5	NP_001139190.1	P0C2W7
CT47B1	XM_017029734.3 link	c.889G>A	p.Gly297Arg	missense_variant	Exon 2 of 3		XP_016885223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CT47B1	ENST00000371311.5 link	c.892G>A	p.Gly298Arg	missense_variant	Exon 2 of 3	5	NM_001145718.3	ENSP00000360360.3		P0C2W7

Frequencies

GnomAD3 genomes

AF:

0.0000627

AC:

AN:

79758

Hom.:

Cov.:

AF XY:

0.0000669

AC XY:

AN XY:

14942

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000193

AC:

AN:

170710

Hom.:

AF XY:

0.000305

AC XY:

AN XY:

62352

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:

0.00136

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000874

AC:

AN:

1075815

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

351007

show subpopulations

Gnomad4 AFR exome

AF:

0.0000383

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000986

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000371

Gnomad4 OTH exome

AF:

0.000154

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000627

AC:

AN:

79758

Hom.:

Cov.:

AF XY:

0.0000669

AC XY:

AN XY:

14942

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:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000270

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.892G>A (p.G298R) alteration is located in exon 2 (coding exon 2) of the CT47B1 gene. This alteration results from a G to A substitution at nucleotide position 892, causing the glycine (G) at amino acid position 298 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CT47B1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.7

DANN

Benign

0.80

DEOGEN2

Benign

0.074

FATHMM_MKL

Benign

0.00014

LIST_S2

Benign

0.52

M_CAP

Benign

0.0060

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.014

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.039

Vest4

0.024

MutPred

0.22

Gain of solvent accessibility (P = 0.0037);

MVP

0.014

MPC

0.0051

ClinPred

0.047

GERP RS

-1.6

Varity_R

0.18

gMVP

0.0016

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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