Variant chr15-73703029-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001024736.2(CD276):c.676G>A(p.Val226Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,613,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

CD276
NM_001024736.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41986287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD276	NM_001024736.2 linkuse as main transcript	c.676G>A	p.Val226Met	missense_variant	4/10	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.676G>A	p.Val226Met	missense_variant	4/10	2	NM_001024736.2	ENSP00000320084	P2	Q5ZPR3-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000133

AC:

AN:

248676

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

134700

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000232

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000178

AC:

260

AN:

1461372

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

122

AN XY:

726946

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:

0.0000464

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000226

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000158

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000409

Hom.:

Bravo

AF:

0.000132

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000238

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.676G>A (p.V226M) alteration is located in exon 4 (coding exon 3) of the CD276 gene. This alteration results from a G to A substitution at nucleotide position 676, causing the valine (V) at amino acid position 226 to be replaced by a methionine (M). 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

-0.31

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

T;T;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.070

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.74

T;T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Benign

-0.40

MutationAssessor

Uncertain

2.1

M;.;M

MutationTaster

Benign

1.0

D;D;N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.37

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.044

D;T;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.99

D;.;D

Vest4

0.51

MVP

0.66

MPC

0.24

ClinPred

0.043

GERP RS

3.3

Varity_R

0.20

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over