X-150777473-C-A

Variant names:

• chrX-150777473-C-A
• rs143706982
• NM_031462.4:c.506G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031462.4(CD99L2):​c.506G>T​(p.Arg169Leu) 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. 14/21 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. R169Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 24)
• Consequence: CD99L2 NM_031462.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 0 publications found

Genes affected

CD99L2 (HGNC:18237): (CD99 molecule like 2) This gene encodes a cell-surface protein that is similar to CD99. A similar protein in mouse functions as an adhesion molecule during leukocyte extravasation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07909709).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD99L2	NM_031462.4	c.506G>T	p.Arg169Leu	missense_variant	Exon 8 of 11	ENST00000370377.8	NP_113650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD99L2	ENST00000370377.8	c.506G>T	p.Arg169Leu	missense_variant	Exon 8 of 11	1	NM_031462.4	ENSP00000359403.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T;.;.;.;.
FATHMM_MKL	Benign	0.056	N
LIST_S2	Uncertain	0.88	D;D;T;D;D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.079	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.;.;.;.
PhyloP100		-0.30
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.6	N;.;N;N;N
REVEL	Benign	0.016
Sift	Benign	0.16	T;.;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.0060	B;.;.;B;B
Vest4		0.18
MutPred		0.28		Loss of methylation at R169 (P = 0.0136);.;.;.;.;
MVP		0.25
MPC		0.10
ClinPred		0.27	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.075
gMVP		0.21
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs143706982; hg19: chrX-149945946;