X-120875109-C-G

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

5
12

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)

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
CT47B1NM_001145718.3 linkc.562G>C p.Gly188Arg missense_variant Exon 1 of 3 ENST00000371311.5 NP_001139190.1 P0C2W7
CT47B1XM_017029734.3 linkc.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
CT47B1ENST00000371311.5 linkc.562G>C p.Gly188Arg missense_variant Exon 1 of 3 5 NM_001145718.3 ENSP00000360360.3 P0C2W7

Frequencies

GnomAD3 genomes
AF:
0.000231
AC:
26
AN:
112499
Hom.:
0
Cov.:
22
AF XY:
0.000260
AC XY:
9
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:
11
AN:
181292
Hom.:
0
AF XY:
0.0000298
AC XY:
2
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:
24
AN:
1096137
Hom.:
0
Cov.:
31
AF XY:
0.0000221
AC XY:
8
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:
26
AN:
112499
Hom.:
0
Cov.:
22
AF XY:
0.000260
AC XY:
9
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.:
0
Bravo
AF:
0.000249
ExAC
AF:
0.0000746
AC:
9
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
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
8.4
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.63
T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.079
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.034
Sift
Uncertain
0.0040
D
Sift4G
Benign
0.18
T
Polyphen
1.0
D
Vest4
0.023
MVP
0.085
MPC
0.024
ClinPred
0.24
T
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.

Other links and lift over

dbSNP: rs752483454; hg19: chrX-120008963; COSMIC: COSV64890371; COSMIC: COSV64890371; API