rs4642

chr17-47292411-A-Cchr17-47292411-A-Gchr17-47292411-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 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. 13/19 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. 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a region_of_interest Cysteine-rich tandem repeats (size 166) in uniprot entity ITB3_HUMAN there are 25 pathogenic changes around while only 4 benign (86%) in NM_000212.3
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31352812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB3	NM_000212.3	c.1533A>C	p.Glu511Asp	missense_variant	10/15	ENST00000559488.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB3	ENST00000559488.7	c.1533A>C	p.Glu511Asp	missense_variant	10/15	1	NM_000212.3	P1
ITGB3	ENST00000696963.1	c.1533A>C	p.Glu511Asp	missense_variant	10/14

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	0.43	P;P;P
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

Publications

LitVar

Other links and lift over

dbSNP: rs4642; hg19: chr17-45369777;