ITGB3 p.Arg6Arg

Variant names:

• chr17-47253876-G-G
• ENST00000559488.7:c.

Your query was ambiguous. Multiple possible variants found:

• chr17-47253877--
• chr17-47253879-G-T
• chr17-47253879-G-C
• chr17-47253879-G-A
• chr17-47253877-C-A
• chr17-47253877-CGG-AGA

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The ENST00000559488.7(ITGB3):​c. variant causes a splice donor, intron 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. The gene ITGB3 is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGB3 ENST00000559488.7 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 0 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]

ITGB3 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 16

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Glanzmann thrombasthenia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Glanzmann thrombasthenia 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• bleeding disorder, platelet-type, 24

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant macrothrombocytopenia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Glanzmann's thrombasthenia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000259753 (HGNC:):

ACMG classification

Specifications for ITGB3 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.04816223 fraction of the gene.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000559488.7. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	ENST00000559488.7	TSL:1 MANE Select	c.		splice_donor intron	N/A	ENSP00000452786.2	P05106-1
	ITGB3	ENST00000571680.1	TSL:1	c.		splice_donor intron	N/A	ENSP00000461626.1	I3L4X8
	ITGB3	ENST00000696963.1		c.		splice_donor intron	N/A	ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.024

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-45331242;