Genetic Variant CT47B1:p.Lys287Asn (chrX-120873935-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145718.3(CT47B1):c.861G>C(p.Lys287Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.00031 ( 0 hom., 0 hem., cov: 13)

Exomes 𝑓: 0.000061 ( 0 hom. 22 hem. )

Failed GnomAD Quality Control

Consequence

CT47B1
NM_001145718.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.420

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010373563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CT47B1	NM_001145718.3 link	c.861G>C	p.Lys287Asn	missense_variant	Exon 2 of 3	ENST00000371311.5	NP_001139190.1	P0C2W7
CT47B1	XM_017029734.3 link	c.858G>C	p.Lys286Asn	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.861G>C	p.Lys287Asn	missense_variant	Exon 2 of 3	5	NM_001145718.3	ENSP00000360360.3		P0C2W7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

82844

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

15048

FAILED QC

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000143

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:

0.000203

AC:

AN:

172686

Hom.:

AF XY:

0.000219

AC XY:

AN XY:

64048

show subpopulations

Gnomad AFR exome

AF:

0.00227

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000529

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000611

AC:

AN:

1080009

Hom.:

Cov.:

AF XY:

0.0000621

AC XY:

AN XY:

354299

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.000171

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:

0.000154

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000314

AC:

AN:

82852

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

15076

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.000143

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:

0.000522

Hom.:

ExAC

AF:

0.000219

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.861G>C (p.K287N) alteration is located in exon 2 (coding exon 2) of the CT47B1 gene. This alteration results from a G to C substitution at nucleotide position 861, causing the lysine (K) at amino acid position 287 to be replaced by an asparagine (N). 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

0.33

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.077

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.46

M_CAP

Benign

0.00079

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

REVEL

Benign

0.11

Sift

Uncertain

0.010

Sift4G

Benign

0.24

Polyphen

0.97

Vest4

0.028

MutPred

0.099

Loss of ubiquitination at K287 (P = 0.0183);

MVP

0.040

MPC

0.0051

ClinPred

0.019

GERP RS

-0.64

Varity_R

0.14

gMVP

0.0046

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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