NM_002414.5:c.363C>T

Variant names:

• chrX-2726261-C-T
• rs1136470
• NM_002414.5:c.363C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002414.5(CD99):​c.363C>T​(p.Ala121Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,601,818 control chromosomes in the GnomAD database, including 15,481 homozygotes. There are 95,822 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A121A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.13 (1258 hom., 8308 hem., cov: 32)
  • Exomes 𝑓: 0.14 (14223 hom. 87514 hem.)
• Consequence: CD99 NM_002414.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.000006554
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BP7: Synonymous conserved (PhyloP=-2.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002414.5. 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
	CD99	NM_002414.5	MANE Select	c.363C>T	p.Ala121Ala	splice_region synonymous	Exon 8 of 10	NP_002405.1	P14209-1
	CD99	NM_001321368.2		c.363C>T	p.Ala121Ala	splice_region synonymous	Exon 8 of 10	NP_001308297.1	A0A096LP69
	CD99	NM_001122898.3		c.315C>T	p.Ala105Ala	splice_region synonymous	Exon 7 of 9	NP_001116370.1	P14209-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD99	ENST00000381192.10	TSL:1 MANE Select	c.363C>T	p.Ala121Ala	splice_region synonymous	Exon 8 of 10	ENSP00000370588.3	P14209-1
	CD99	ENST00000381184.6	TSL:5	c.363C>T	p.Ala121Ala	splice_region synonymous	Exon 8 of 10	ENSP00000370579.1	A8MQT7
	CD99	ENST00000611428.5	TSL:1	c.363C>T	p.Ala121Ala	splice_region synonymous	Exon 8 of 11	ENSP00000479999.1	P14209-2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19220 AN: 151928 Hom.: 1261 Cov.: 32

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.154

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.147

GnomAD2 exomes AF: 0.143 AC: 35827 AN: 250760 AF XY: 0.129

Gnomad AFR exome AF: 0.0886

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.0777

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.138 AC: 199616 AN: 1449770 Hom.: 14223 Cov.: 30 AF XY: 0.121 AC XY: 87514 AN XY: 721614

African (AFR) AF: 0.0899 AC: 2988 AN: 33236

American (AMR) AF: 0.225 AC: 10041 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3985 AN: 26046

East Asian (EAS) AF: 0.0576 AC: 2284 AN: 39642

South Asian (SAS) AF: 0.146 AC: 12510 AN: 85962

European-Finnish (FIN) AF: 0.128 AC: 6815 AN: 53410

Middle Eastern (MID) AF: 0.173 AC: 733 AN: 4244

European-Non Finnish (NFE) AF: 0.138 AC: 151942 AN: 1102654

Other (OTH) AF: 0.139 AC: 8318 AN: 59898

GnomAD4 genome AF: 0.126 AC: 19224 AN: 152048 Hom.: 1258 Cov.: 32 AF XY: 0.112 AC XY: 8308 AN XY: 74320

African (AFR) AF: 0.0901 AC: 3739 AN: 41482

American (AMR) AF: 0.167 AC: 2543 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3466

East Asian (EAS) AF: 0.0799 AC: 413 AN: 5168

South Asian (SAS) AF: 0.141 AC: 679 AN: 4812

European-Finnish (FIN) AF: 0.113 AC: 1201 AN: 10582

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.143 AC: 9716 AN: 67954

Other (OTH) AF: 0.145 AC: 306 AN: 2110

Bravo AF: 0.131

EpiCase AF: 0.139

EpiControl AF: 0.139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.013
DANN	Benign	0.53
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000066
dbscSNV1_RF	Benign	0.0
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: rs1136470; hg19: chrX-2644302; COSMIC: COSV66989192; COSMIC: COSV66989192;