dbSNP rs141119771: CD276:p.Val112Met (chr15-73702509-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001329629.2(CD276):c.-105G>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000366 in 1,613,042 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

CD276
NM_001329629.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD276	NM_001024736.2 link	c.334G>A	p.Val112Met	missense_variant	Exon 3 of 10	ENST00000318443.10	NP_001019907.1	Q5ZPR3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD276	ENST00000318443.10 link	c.334G>A	p.Val112Met	missense_variant	Exon 3 of 10	2	NM_001024736.2	ENSP00000320084.5		Q5ZPR3-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000925

AC:

AN:

248706

Hom.:

AF XY:

0.0000667

AC XY:

AN XY:

134858

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:

0.00

Gnomad FIN exome

AF:

0.0000944

Gnomad NFE exome

AF:

0.000179

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1460836

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

726806

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:

0.0000116

Gnomad4 FIN exome

AF:

0.0000761

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.334G>A (p.V112M) alteration is located in exon 3 (coding exon 2) of the CD276 gene. This alteration results from a G to A substitution at nucleotide position 334, causing the valine (V) at amino acid position 112 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

Pathogenic

0.62

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

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

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.96

.;D;D;D;D;D;D;D;.

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.74

D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.12

MutationAssessor

Pathogenic

3.2

.;M;M;.;.;M;.;.;M

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-2.8

D;N;N;D;D;N;D;D;N

REVEL

Uncertain

0.54

Sift

Uncertain

0.0020

D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D;D;D;D;D

Polyphen

1.0, 1.0

.;D;D;.;.;D;.;.;D

Vest4

0.68, 0.77, 0.77

MVP

0.62

MPC

0.61

ClinPred

0.71

GERP RS

2.9

Varity_R

0.37

gMVP

0.35

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

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