NM_001024736.2:c.370G>C

Variant names:

• chr15-73702545-G-C
• NM_001024736.2:c.370G>C

Variant summary

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

The NM_001024736.2(CD276):​c.370G>C​(p.Val124Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,564 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CD276 NM_001024736.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.95

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

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	c.370G>C	p.Val124Leu	missense_variant	Exon 3 of 10	ENST00000318443.10	NP_001019907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD276	ENST00000318443.10	c.370G>C	p.Val124Leu	missense_variant	Exon 3 of 10	2	NM_001024736.2	ENSP00000320084.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459564 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726204

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T;T;.;T;.;.;T;T;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	.;T;D;T;T;T;T;T;.
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.59	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	.;M;M;.;.;M;.;.;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.80	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.017	D;T;T;D;D;T;D;T;T
Sift4G	Uncertain	0.025	D;T;D;D;D;T;D;D;D
Polyphen		0.95, 1.0, 0.94	.;P;D;.;.;P;.;.;D
Vest4		0.54, 0.46, 0.55, 0.45
MutPred		0.66		Loss of catalytic residue at V124 (P = 0.0725);Loss of catalytic residue at V124 (P = 0.0725);Loss of catalytic residue at V124 (P = 0.0725);Loss of catalytic residue at V124 (P = 0.0725);Loss of catalytic residue at V124 (P = 0.0725);Loss of catalytic residue at V124 (P = 0.0725);Loss of catalytic residue at V124 (P = 0.0725);Loss of catalytic residue at V124 (P = 0.0725);Loss of catalytic residue at V124 (P = 0.0725);
MVP		0.27
MPC		0.13
ClinPred		0.67	D
GERP RS		1.9
Varity_R		0.20
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-73994886;