X-120874935-C-A

Variant names:

• chrX-120874935-C-A
• rs377302141
• NM_001145718.3:c.736G>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.736G>T​(p.Ala246Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,208,663 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 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. A246T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000039 (0 hom. 20 hem.)
• Consequence: CT47B1 NM_001145718.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.412
• Publications: 0 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=0.023220599).
• BS2: High Hemizygotes in GnomAdExome4 at 20 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.736G>T	p.Ala246Ser	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.736G>T	p.Ala246Ser	missense	Exon 1 of 3	ENSP00000360360.3	P0C2W7

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112349 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: 0.000561

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

GnomAD2 exomes AF: 0.0000439 AC: 8 AN: 182191 AF XY: 0.000104

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000392 AC: 43 AN: 1096262 Hom.: 0 Cov.: 31 AF XY: 0.0000552 AC XY: 20 AN XY: 362222

African (AFR) AF: 0.0000379 AC: 1 AN: 26372

American (AMR) AF: 0.00 AC: 0 AN: 35195

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

East Asian (EAS) AF: 0.000298 AC: 9 AN: 30194

South Asian (SAS) AF: 0.000407 AC: 22 AN: 54078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3561

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841340

Other (OTH) AF: 0.000239 AC: 11 AN: 45979

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112401 Hom.: 0 Cov.: 22 AF XY: 0.0000289 AC XY: 1 AN XY: 34603

African (AFR) AF: 0.00 AC: 0 AN: 31025

American (AMR) AF: 0.00 AC: 0 AN: 10718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.000562 AC: 2 AN: 3556

South Asian (SAS) AF: 0.00 AC: 0 AN: 2724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53136

Other (OTH) AF: 0.00 AC: 0 AN: 1523

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000419 AC: 1

ExAC AF: 0.0000331 AC: 4

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	0.10
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.066
DANN	Benign	0.84
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.00065	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.41
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.0060
Sift	Benign	0.70	T
Sift4G	Benign	0.12	T
Polyphen		0.042	B
Vest4		0.040
MVP		0.014
MPC		0.0056
ClinPred		0.012	T
GERP RS		0.69
Varity_R		0.043
gMVP		0.0041
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: rs377302141; hg19: chrX-120008789;