17-47292411-A-C

Variant names:

• chr17-47292411-A-C
• rs4642
• NM_000212.3:c.1533A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000212.3(ITGB3):​c.1533A>C​(p.Glu511Asp) 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. 15/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E511K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITGB3 NM_000212.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 33 publications found

Genes affected

ITGB3 (HGNC:6156): (integrin subunit beta 3) The ITGB3 protein product is the integrin beta chain beta 3. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. A given chain may combine with multiple partners resulting in different integrins. Integrin beta 3 is found along with the alpha IIb chain in platelets. Integrins are known to participate in cell adhesion as well as cell-surface mediated signalling. [provided by RefSeq, Jul 2008]

ENSG00000259753 (HGNC:):

EFCAB13-DT (HGNC:55338): (EFCAB13 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31352812).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000212.3. 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
	ITGB3	NM_000212.3	MANE Select	c.1533A>C	p.Glu511Asp	missense	Exon 10 of 15	NP_000203.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	ENST00000559488.7	TSL:1 MANE Select	c.1533A>C	p.Glu511Asp	missense	Exon 10 of 15	ENSP00000452786.2	P05106-1
	ENSG00000259753	ENST00000560629.1	TSL:2	n.1497A>C		non_coding_transcript_exon	Exon 10 of 18	ENSP00000456711.2	H3BM21
	ITGB3	ENST00000696963.1		c.1533A>C	p.Glu511Asp	missense	Exon 10 of 14	ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	-0.15	N
PhyloP100		2.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.62	N
Sift	Benign	0.59	T
Sift4G	Benign	0.62	T
Polyphen		0.0050	B
Vest4		0.14
MutPred		0.19		Loss of glycosylation at P514 (P = 0.2355)
MVP		0.89
MPC		0.37
ClinPred		0.084	T
GERP RS		5.4
Varity_R		0.22
gMVP		0.56

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: rs4642; hg19: chr17-45369777;