chrX-120875015-G-A

Variant names:

• chrX-120875015-G-A
• rs750373515
• NM_001145718.3:c.656C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001145718.3(CT47B1):​c.656C>T​(p.Ala219Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,208,579 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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. A219T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000021 (0 hom. 12 hem.)
• Consequence: CT47B1 NM_001145718.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.19
• Publications: 3 publications found

Genes affected

CT47B1 (HGNC:33293): (cancer/testis antigen family 47 member B1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04920304).
• BS2: High Hemizygotes in GnomAdExome4 at 12 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145718.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CT47B1	NM_001145718.3	MANE Select	c.656C>T	p.Ala219Val	missense	Exon 1 of 3	NP_001139190.1	P0C2W7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CT47B1	ENST00000371311.5	TSL:5 MANE Select	c.656C>T	p.Ala219Val	missense	Exon 1 of 3	ENSP00000360360.3	P0C2W7

Frequencies

GnomAD3 genomes AF: 0.0000267 AC: 3 AN: 112324 Hom.: 0 Cov.: 22

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: 0.0000565

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000329 AC: 6 AN: 182097 AF XY: 0.0000889

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000723

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000210 AC: 23 AN: 1096201 Hom.: 0 Cov.: 31 AF XY: 0.0000331 AC XY: 12 AN XY: 362251

African (AFR) AF: 0.0000759 AC: 2 AN: 26355

American (AMR) AF: 0.00 AC: 0 AN: 35199

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19371

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30192

South Asian (SAS) AF: 0.00 AC: 0 AN: 54062

European-Finnish (FIN) AF: 0.0000248 AC: 1 AN: 40282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3332

European-Non Finnish (NFE) AF: 0.0000178 AC: 15 AN: 841438

Other (OTH) AF: 0.0000870 AC: 4 AN: 45970

GnomAD4 genome AF: 0.0000267 AC: 3 AN: 112378 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34598

African (AFR) AF: 0.00 AC: 0 AN: 31008

American (AMR) AF: 0.00 AC: 0 AN: 10754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.00 AC: 0 AN: 2739

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000565 AC: 3 AN: 53085

Other (OTH) AF: 0.00 AC: 0 AN: 1534

Alfa AF: 0.000130 Hom.: 1

Bravo AF: 0.00000378

ExAC AF: 0.0000662 AC: 8

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.41
DANN	Benign	0.97
DEOGEN2	Benign	0.026	T
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.040
Sift	Benign	0.50	T
Sift4G	Benign	0.49	T
Polyphen		0.33	B
Vest4		0.056
MutPred		0.14		Loss of glycosylation at P218 (P = 0.0966)
MVP		0.22
MPC		0.0055
ClinPred		0.027	T
GERP RS		0.32
Varity_R		0.041
gMVP		0.016
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs750373515; hg19: chrX-120008869; COSMIC: COSV64890986; COSMIC: COSV64890986;