Genetic Variant ITGB3:p.Ala12Val (chr17-47253896-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000212.3(ITGB3):c.35C>T(p.Ala12Val) 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. 12/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A12E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ITGB3
NM_000212.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.630

Publications

0 publications found

Variant links:

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

ITGB3 links:

ENSG00000259753 (HGNC:):

ENSG00000259753 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18428814).

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.35C>T	p.Ala12Val	missense	Exon 1 of 15	NP_000203.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGB3	ENST00000559488.7	TSL:1 MANE Select	c.35C>T	p.Ala12Val	missense	Exon 1 of 15	ENSP00000452786.2	P05106-1
ITGB3	ENST00000571680.1	TSL:1	c.35C>T	p.Ala12Val	missense	Exon 1 of 9	ENSP00000461626.1	I3L4X8
ITGB3	ENST00000696963.1		c.35C>T	p.Ala12Val	missense	Exon 1 of 14	ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1192246

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

581804

African (AFR)

AF:

0.00

AC:

AN:

24904

American (AMR)

AF:

0.00

AC:

AN:

18902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19462

East Asian (EAS)

AF:

0.00

AC:

AN:

27084

South Asian (SAS)

AF:

0.00

AC:

AN:

46984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3478

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

975226

Other (OTH)

AF:

0.00

AC:

AN:

47686

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PhyloP100

0.63

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.79

Sift

Benign

0.29

Sift4G

Benign

0.67

Polyphen

0.0010

Vest4

0.39

MutPred

0.35

Loss of disorder (P = 0.0925)

MVP

0.91

MPC

0.40

ClinPred

0.095

GERP RS

2.1

PromoterAI

0.098

Neutral

(source)

Varity_R

0.047

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over