NM_020404.3:c.1957C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020404.3(CD248):​c.1957C>T​(p.Pro653Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,417,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CD248
NM_020404.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.156

Publications

0 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05052641).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD248NM_020404.3 linkc.1957C>T p.Pro653Ser missense_variant Exon 1 of 1 ENST00000311330.4 NP_065137.1 Q9HCU0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD248ENST00000311330.4 linkc.1957C>T p.Pro653Ser missense_variant Exon 1 of 1 6 NM_020404.3 ENSP00000308117.3 Q9HCU0-1
ENSG00000254458ENST00000534065.1 linkn.140+2079G>A intron_variant Intron 1 of 1 4
ENSG00000254756ENST00000820635.1 linkn.134+2908G>A intron_variant Intron 1 of 3
ENSG00000254756ENST00000820636.1 linkn.96+2908G>A intron_variant Intron 1 of 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000212
AC:
3
AN:
1417446
Hom.:
0
Cov.:
30
AF XY:
0.00000286
AC XY:
2
AN XY:
699776
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32558
American (AMR)
AF:
0.00
AC:
0
AN:
40912
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22658
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39346
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78514
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
50432
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5536
European-Non Finnish (NFE)
AF:
0.00000275
AC:
3
AN:
1089036
Other (OTH)
AF:
0.00
AC:
0
AN:
58454
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.542
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000371
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 29, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1957C>T (p.P653S) alteration is located in exon 1 (coding exon 1) of the CD248 gene. This alteration results from a C to T substitution at nucleotide position 1957, causing the proline (P) at amino acid position 653 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
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
3.2
DANN
Benign
0.56
DEOGEN2
Benign
0.061
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.085
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.051
T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
0.63
N
PhyloP100
0.16
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.020
N
REVEL
Benign
0.12
Sift
Benign
0.40
T
Sift4G
Benign
0.46
T
Polyphen
0.0010
B
Vest4
0.054
MVP
0.26
MPC
0.35
ClinPred
0.047
T
GERP RS
0.39
Varity_R
0.022
gMVP
0.31
Mutation Taster
=94/6
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

Publications

Other links and lift over

dbSNP: rs1854527944; hg19: chr11-66082542; API