X-120875015-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145718.3(CT47B1):​c.656C>A​(p.Ala219Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: CT47B1 NM_001145718.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 3 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052518874).

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>A	p.Ala219Glu	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>A	p.Ala219Glu	missense	Exon 1 of 3	ENSP00000360360.3	P0C2W7

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 182097 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.12e-7 AC: 1 AN: 1096202 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362252

African (AFR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 30192

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40282

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841438

Other (OTH) AF: 0.00 AC: 0 AN: 45971

GnomAD4 genome Cov.: 22

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.13
DANN	Benign	0.78
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.68	N
PhyloP100		-1.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.030
Sift	Benign	0.34	T
Sift4G	Benign	0.16	T
Polyphen		0.52	P
Vest4		0.039
MutPred		0.15		Gain of solvent accessibility (P = 0.005)
MVP		0.22
MPC		0.0051
ClinPred		0.050	T
GERP RS		0.32
Varity_R		0.16
gMVP		0.020
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;