NM_001024736.2:c.1285G>C

Variant names:

• chr15-73704388-G-C
• rs62641691
• NM_001024736.2:c.1285G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001024736.2(CD276):​c.1285G>C​(p.Val429Leu) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V429M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CD276 NM_001024736.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16110998).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024736.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD276	NM_001024736.2	MANE Select	c.1285G>C	p.Val429Leu	missense	Exon 6 of 10	NP_001019907.1	Q5ZPR3-1
	CD276	NM_001329629.2		c.847G>C	p.Val283Leu	missense	Exon 5 of 9	NP_001316558.1	A0A0C4DGH0
	CD276	NM_001329628.2		c.631G>C	p.Val211Leu	missense	Exon 4 of 8	NP_001316557.1	Q5ZPR3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD276	ENST00000318443.10	TSL:2 MANE Select	c.1285G>C	p.Val429Leu	missense	Exon 6 of 10	ENSP00000320084.5	Q5ZPR3-1
	CD276	ENST00000564751.5	TSL:1	c.631G>C	p.Val211Leu	missense	Exon 3 of 7	ENSP00000454940.1	Q5ZPR3-2
	CD276	ENST00000559073.1	TSL:1	n.190G>C		non_coding_transcript_exon	Exon 1 of 6	ENSP00000453842.1	H0YN29

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 3

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.74	N
PhyloP100		0.40
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.12
Sift	Benign	0.69	T
Sift4G	Benign	0.15	T
Polyphen		0.0010	B
Vest4		0.27
MutPred		0.67		Loss of sheet (P = 0.0817)
MVP		0.53
MPC		0.13
ClinPred		0.074	T
GERP RS		2.0
PromoterAI		-0.0058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.039
gMVP		0.29

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

Other links and lift over

dbSNP: rs62641691; hg19: chr15-73996729;