Variant chr15-73702341-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001024736.2(CD276):c.166C>T(p.Pro56Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CD276
NM_001024736.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.849

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]

CD276 links:

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ACMG classification

Classification made for transcript

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=0.07314223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD276	NM_001024736.2 linkuse as main transcript	c.166C>T	p.Pro56Ser	missense_variant	3/10	ENST00000318443.10	NP_001019907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD276	ENST00000318443.10 linkuse as main transcript	c.166C>T	p.Pro56Ser	missense_variant	3/10	2	NM_001024736.2	ENSP00000320084	P2	Q5ZPR3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Jan 31, 2023

The c.166C>T (p.P56S) alteration is located in exon 3 (coding exon 2) of the CD276 gene. This alteration results from a C to T substitution at nucleotide position 166, causing the proline (P) at amino acid position 56 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

0.090

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.013

T;T;.;T;.;.;.;T;T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.83

.;T;D;D;D;T;D;D;D;.

M_CAP

Benign

0.012

MetaRNN

Benign

0.073

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.60

.;N;N;.;.;N;.;.;.;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.69

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.046

Sift

Benign

0.12

T;T;T;T;T;T;D;T;T;T

Sift4G

Benign

0.21

T;T;T;T;T;T;T;T;T;T

Polyphen

0.032, 0.31, 0.025

.;B;B;.;.;B;.;.;.;B

Vest4

0.13, 0.11, 0.13, 0.12

MutPred

0.39

Gain of glycosylation at P56 (P = 0.092);Gain of glycosylation at P56 (P = 0.092);Gain of glycosylation at P56 (P = 0.092);Gain of glycosylation at P56 (P = 0.092);Gain of glycosylation at P56 (P = 0.092);Gain of glycosylation at P56 (P = 0.092);.;Gain of glycosylation at P56 (P = 0.092);Gain of glycosylation at P56 (P = 0.092);Gain of glycosylation at P56 (P = 0.092);

MVP

0.22

MPC

0.61

ClinPred

0.16

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.050

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over