7-80646754-G-C

Variant names:

• chr7-80646754-G-C
• rs13306227
• NM_001001548.3:c.14G>C

Variant summary

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

The NM_000072.3(CD36):​c.14G>C​(p.Arg5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R5Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD36 NM_000072.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 2 publications found

Genes affected

CD36 (HGNC:1663): (CD36 molecule (CD36 blood group)) The protein encoded by this gene is the fourth major glycoprotein of the platelet surface and serves as a receptor for thrombospondin in platelets and various cell lines. Since thrombospondins are widely distributed proteins involved in a variety of adhesive processes, this protein may have important functions as a cell adhesion molecule. It binds to collagen, thrombospondin, anionic phospholipids and oxidized LDL. It directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes and it binds long chain fatty acids and may function in the transport and/or as a regulator of fatty acid transport. Mutations in this gene cause platelet glycoprotein deficiency. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2014]

CD36 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 10

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000072.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD36	NM_001001548.3	MANE Select	c.14G>C	p.Arg5Pro	missense	Exon 3 of 15	NP_001001548.1
	CD36	NM_000072.3		c.14G>C	p.Arg5Pro	missense	Exon 3 of 14	NP_000063.2
	CD36	NM_001001547.3		c.14G>C	p.Arg5Pro	missense	Exon 3 of 14	NP_001001547.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD36	ENST00000447544.7	TSL:5 MANE Select	c.14G>C	p.Arg5Pro	missense	Exon 3 of 15	ENSP00000415743.2
	CD36	ENST00000309881.11	TSL:1	c.14G>C	p.Arg5Pro	missense	Exon 3 of 14	ENSP00000308165.7
	CD36	ENST00000394788.7	TSL:1	c.14G>C	p.Arg5Pro	missense	Exon 3 of 14	ENSP00000378268.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.0091
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.37
Sift	Benign	0.14	T
Sift4G	Benign	0.14	T
Polyphen		0.97	D
Vest4		0.72
MutPred		0.77		Loss of helix (P = 0.0626)
MVP		0.24
MPC		0.00036
ClinPred		0.92	D
GERP RS		5.5
PromoterAI		-0.075	Neutral
Varity_R		0.54
gMVP		0.83
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs13306227; hg19: chr7-80276070;