X-2731325-T-C

Variant names:

• chrX-2731325-T-C
• rs1684022
• NM_002414.5:c.475+4952T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000381192.10(CD99):​c.475+4952T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 152,104 control chromosomes in the GnomAD database, including 1,318 homozygotes. There are 5,167 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.073 (1318 hom., 5167 hem., cov: 32)
• Consequence: CD99 ENST00000381192.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37
• Publications: 0 publications found

Genes affected

CD99 (HGNC:7082): (CD99 molecule (Xg blood group)) The protein encoded by this gene is a cell surface glycoprotein involved in leukocyte migration, T-cell adhesion, ganglioside GM1 and transmembrane protein transport, and T-cell death by a caspase-independent pathway. In addition, the encoded protein may have the ability to rearrange the actin cytoskeleton and may also act as an oncosuppressor in osteosarcoma. This gene is found in the pseudoautosomal region of chromosomes X and Y and escapes X-chromosome inactivation. There is a related pseudogene located immediately adjacent to this locus. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381192.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD99	NM_002414.5	MANE Select	c.475+4952T>C		intron	N/A	NP_002405.1
	CD99	NM_001321368.2		c.475+4952T>C		intron	N/A	NP_001308297.1
	CD99	NM_001122898.3		c.427+4952T>C		intron	N/A	NP_001116370.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD99	ENST00000381192.10	TSL:1 MANE Select	c.475+4952T>C		intron	N/A	ENSP00000370588.3
	CD99	ENST00000381184.6	TSL:5	c.527-2032T>C		intron	N/A	ENSP00000370579.1
	CD99	ENST00000611428.5	TSL:1	c.476-2032T>C		intron	N/A	ENSP00000479999.1

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11051 AN: 151986 Hom.: 1311 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0237

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.0475

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0729 AC: 11087 AN: 152104 Hom.: 1318 Cov.: 32 AF XY: 0.0695 AC XY: 5167 AN XY: 74372

African (AFR) AF: 0.251 AC: 10395 AN: 41444

American (AMR) AF: 0.0236 AC: 361 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3464

East Asian (EAS) AF: 0.0221 AC: 114 AN: 5162

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00125 AC: 85 AN: 68000

Other (OTH) AF: 0.0470 AC: 99 AN: 2108

Bravo AF: 0.0822

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.13
PhyloP100		-2.4

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: rs1684022; hg19: chrX-2649366;