Genetic Variant CT47B1:p.Ala232Ser (chrX-120874977-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001145718.3(CT47B1):c.694G>T(p.Ala232Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000314 in 1,208,900 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A232T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000044 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000030 ( 0 hom. 14 hem. )

Consequence

CT47B1
NM_001145718.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.09

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038754046).

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.694G>T	p.Ala232Ser	missense_variant	Exon 1 of 3	ENST00000371311.5	NP_001139190.1	P0C2W7
CT47B1	XM_017029734.3 link	c.694G>T	p.Ala232Ser	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.694G>T	p.Ala232Ser	missense_variant	Exon 1 of 3	5	NM_001145718.3	ENSP00000360360.3		P0C2W7

Frequencies

GnomAD3 genomes

AF:

0.0000444

AC:

AN:

112587

Hom.:

Cov.:

AF XY:

0.0000575

AC XY:

AN XY:

34775

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000186

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:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000329

AC:

AN:

182585

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

67553

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000525

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000369

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1096313

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

362289

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000852

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:

0.0000333

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000444

AC:

AN:

112587

Hom.:

Cov.:

AF XY:

0.0000575

AC XY:

AN XY:

34775

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000186

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000564

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ExAC

AF:

0.0000414

AC:

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.694G>T (p.A232S) alteration is located in exon 1 (coding exon 1) of the CT47B1 gene. This alteration results from a G to T substitution at nucleotide position 694, causing the alanine (A) at amino acid position 232 to be replaced by a serine (S). 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

0.096

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.36

DANN

Benign

0.83

DEOGEN2

Benign

0.012

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.30

M_CAP

Benign

0.0032

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.93

REVEL

Benign

0.011

Sift

Benign

0.73

Sift4G

Benign

0.083

Polyphen

0.090

Vest4

0.031

MVP

0.014

MPC

0.0056

ClinPred

0.022

GERP RS

-2.9

Varity_R

0.058

gMVP

0.0089

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