NM_002414.5:c.475+4952T>C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002414.5(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 NM_002414.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD99	NM_002414.5	c.475+4952T>C		intron_variant	Intron 8 of 9	ENST00000381192.10	NP_002405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD99	ENST00000381192.10	c.475+4952T>C		intron_variant	Intron 8 of 9	1	NM_002414.5	ENSP00000370588.3
CD99	ENST00000381184.6	c.527-2032T>C		intron_variant	Intron 9 of 9	5		ENSP00000370579.1

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11051 AN: 151986 Hom.: 1311 Cov.: 32 AF XY: 0.0693 AC XY: 5142 AN XY: 74244

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

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.0236

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0221

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00125

Gnomad4 OTH AF: 0.0470

Bravo AF: 0.0822

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Other links and lift over

dbSNP: rs1684022; hg19: chrX-2649366;