Variant summary

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

The NM_000212.3(ITGB3):c.1373A>G(p.Asp458Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as association (★). Synonymous variant affecting the same amino acid position (i.e. D458D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ITGB3
NM_000212.3 missense

Scores

Clinical Significance

association criteria provided, single submitter O:1

Conservation

PhyloP100: 1.81

Publications

1 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 links:

ENSG00000259753 (HGNC:):

ENSG00000259753 links:

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

EFCAB13-DT links:

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ACMG classification

Classification was made for transcript

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

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	NM_000212.3	MANE Select	c.1373A>G	p.Asp458Gly	missense	Exon 10 of 15	NP_000203.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ITGB3	ENST00000559488.7	TSL:1 MANE Select	c.1373A>G	p.Asp458Gly	missense	Exon 10 of 15	ENSP00000452786.2
ENSG00000259753	ENST00000560629.1	TSL:2	n.1337A>G		non_coding_transcript_exon	Exon 10 of 18	ENSP00000456711.2
ITGB3	ENST00000696963.1		c.1373A>G	p.Asp458Gly	missense	Exon 10 of 14	ENSP00000513002.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:association

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Fetal and neonatal alloimmune thrombocytopenia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.72

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.32

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.4

PhyloP100

1.8

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.5

Sift

Benign

0.38

Sift4G

Benign

0.38

Polyphen

0.094

Vest4

0.43

MutPred

0.52

Loss of catalytic residue at D458 (P = 0.1091)

MVP

0.72

MPC

0.62

ClinPred

0.38

GERP RS

5.4

Varity_R

0.26

gMVP

0.70

Mutation Taster

=61/39

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr17-47292251-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over