17-47283395-T-A

Variant names:

• chr17-47283395-T-A
• NM_000212.3:c.207T>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000212.3(ITGB3):​c.207T>A​(p.Asn69Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGB3 NM_000212.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0610

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3876605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3	c.207T>A	p.Asn69Lys	missense_variant	Exon 3 of 15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7	c.207T>A	p.Asn69Lys	missense_variant	Exon 3 of 15	1	NM_000212.3	ENSP00000452786.2
ITGB3	ENST00000571680.1	c.207T>A	p.Asn69Lys	missense_variant	Exon 3 of 9	1		ENSP00000461626.1
ENSG00000259753	ENST00000560629.1	n.171T>A		non_coding_transcript_exon_variant	Exon 3 of 18	2		ENSP00000456711.2
ITGB3	ENST00000696963.1	c.207T>A	p.Asn69Lys	missense_variant	Exon 3 of 14			ENSP00000513002.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Feb 20, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 69 of the ITGB3 protein (p.Asn69Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ITGB3-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ITGB3 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.82	D;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	0.052	D
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.6	D;.
Sift	Benign	0.074	T;.
Sift4G	Benign	0.42	T;T
Polyphen		0.98	D;.
Vest4		0.35
MutPred		0.58		Gain of ubiquitination at N69 (P = 0.0177);Gain of ubiquitination at N69 (P = 0.0177);
MVP		0.95
MPC		1.1
ClinPred		0.97	D
GERP RS		-1.6
Varity_R		0.48
gMVP		0.90

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: chr17-45360761;