3-112345081-C-T

Position:

• chr3-112345081-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005944.7(CD200):​c.214C>T​(p.Pro72Ser) 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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD200 NM_005944.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

Genes affected

CD200 (HGNC:7203): (CD200 molecule) This gene encodes a type I membrane glycoprotein containing two extracellular immunoglobulin domains, a transmembrane and a cytoplasmic domain. This gene is expressed by various cell types, including B cells, a subset of T cells, thymocytes, endothelial cells, and neurons. The encoded protein plays an important role in immunosuppression and regulation of anti-tumor activity. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22188866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD200	NM_005944.7	c.214C>T	p.Pro72Ser	missense_variant	3/6	ENST00000315711.12	NP_005935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD200	ENST00000315711.12	c.214C>T	p.Pro72Ser	missense_variant	3/6	1	NM_005944.7	ENSP00000312766.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.289C>T (p.P97S) alteration is located in exon 4 (coding exon 4) of the CD200 gene. This alteration results from a C to T substitution at nucleotide position 289, causing the proline (P) at amino acid position 97 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;.;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	.;.;M
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.5	.;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0070	.;D;D
Sift4G	Benign	0.28	T;D;T
Polyphen		0.15, 1.0	.;B;D
Vest4		0.037, 0.042
MutPred		0.38		.;.;Gain of disorder (P = 0.079);
MVP		0.47
MPC		0.69
ClinPred		0.73	D
GERP RS		6.2
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-112063928;