11-66315008-C-G

Variant names:

• chr11-66315008-C-G
• rs1854527275
• NM_020404.3:c.2020G>C

Variant summary

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

The NM_020404.3(CD248):​c.2020G>C​(p.Ala674Pro) 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. 15/22 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: CD248 NM_020404.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00100
• Publications: 0 publications found

Genes affected

CD248 (HGNC:18219): (CD248 molecule) Predicted to enable extracellular matrix binding activity and extracellular matrix protein binding activity. Predicted to be involved in cell migration. Predicted to act upstream of or within several processes, including anatomical structure regression; lymph node development; and positive regulation of endothelial cell apoptotic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000254458 (HGNC:):

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=0.1694887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD248	NM_020404.3	c.2020G>C	p.Ala674Pro	missense_variant	Exon 1 of 1	ENST00000311330.4	NP_065137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD248	ENST00000311330.4	c.2020G>C	p.Ala674Pro	missense_variant	Exon 1 of 1	6	NM_020404.3	ENSP00000308117.3
ENSG00000254458	ENST00000534065.1	n.140+2016C>G		intron_variant	Intron 1 of 1	4
ENSG00000254756	ENST00000820635.1	n.134+2845C>G		intron_variant	Intron 1 of 3
ENSG00000254756	ENST00000820636.1	n.96+2845C>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2020G>C (p.A674P) alteration is located in exon 1 (coding exon 1) of the CD248 gene. This alteration results from a G to C substitution at nucleotide position 2020, causing the alanine (A) at amino acid position 674 to be replaced by a proline (P). 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
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	0.00098	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.0010
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.27
Sift	Benign	0.14	T
Sift4G	Benign	0.35	T
Polyphen		0.92	P
Vest4		0.44
MutPred		0.18		Gain of glycosylation at A674 (P = 0.0443);
MVP		0.54
MPC		1.1
ClinPred		0.48	T
GERP RS		1.3
Varity_R		0.067
gMVP		0.25
Mutation Taster		=82/18	polymorphism

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: rs1854527275; hg19: chr11-66082479;