15-73702257-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001024736.2(CD276):​c.82G>T​(p.Ala28Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CD276
NM_001024736.2 missense, splice_region

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.11
Variant links:
Genes affected
CD276 (HGNC:19137): (CD276 molecule) The protein encoded by this gene belongs to the immunoglobulin superfamily, and thought to participate in the regulation of T-cell-mediated immune response. Studies show that while the transcript of this gene is ubiquitously expressed in normal tissues and solid tumors, the protein is preferentially expressed only in tumor tissues. Additionally, it was observed that the 3' UTR of this transcript contains a target site for miR29 microRNA, and there is an inverse correlation between the expression of this protein and miR29 levels, suggesting regulation of expression of this gene product by miR29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34665644).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CD276NM_001024736.2 linkuse as main transcriptc.82G>T p.Ala28Ser missense_variant, splice_region_variant 3/10 ENST00000318443.10 NP_001019907.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CD276ENST00000318443.10 linkuse as main transcriptc.82G>T p.Ala28Ser missense_variant, splice_region_variant 3/102 NM_001024736.2 ENSP00000320084 P2Q5ZPR3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000418
AC:
1
AN:
239430
Hom.:
0
AF XY:
0.00000766
AC XY:
1
AN XY:
130536
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000337
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000275
AC:
4
AN:
1453390
Hom.:
0
Cov.:
32
AF XY:
0.00000277
AC XY:
2
AN XY:
722132
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000351
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.03e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 06, 2023The c.82G>T (p.A28S) alteration is located in exon 3 (coding exon 2) of the CD276 gene. This alteration results from a G to T substitution at nucleotide position 82, causing the alanine (A) at amino acid position 28 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
0.093
BayesDel_addAF
Benign
-0.056
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.011
T;T;.;T;.;.;.;.;T;T;.
Eigen
Benign
0.12
Eigen_PC
Benign
0.021
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.81
.;T;D;D;D;T;D;D;D;D;.
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.35
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.7
.;M;M;.;.;M;.;.;.;.;M
MutationTaster
Benign
1.0
D;D;D;N;N
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.090
N;N;N;N;N;N;N;D;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.16
T;D;T;T;T;T;T;D;T;T;T
Sift4G
Benign
0.23
T;D;D;T;T;D;D;D;T;T;D
Polyphen
0.94, 0.99, 0.93
.;P;D;.;.;P;.;.;.;.;D
Vest4
0.14, 0.13, 0.14
MutPred
0.50
Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);.;Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP
0.65
MPC
0.57
ClinPred
0.61
D
GERP RS
2.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.075
gMVP
0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs769865072; hg19: chr15-73994598; API