rs1555572829

Variant names:

• chr17-47292251-A-G
• rs1555572829
• NM_000212.3:c.1373A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-47292251-A-G
• chr17-47292251-A-T

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
• Clinical Significance: association criteria provided, single submitter O:1
• Conservation: PhyloP100: 1.81
• Publications: 1 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]

ENSG00000259753 (HGNC:):

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

ACMG classification

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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.: 32

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: association

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.72	D
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.8
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N
Sift	Benign	0.38	T
Sift4G	Benign	0.38	T
Polyphen		0.094	B
Vest4		0.43
MutPred		0.52		Loss of catalytic residue at D458 (P = 0.1091)
MVP		0.72
MPC		0.62
ClinPred		0.38	T
GERP RS		5.4
Varity_R		0.26
gMVP		0.70
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs1555572829; hg19: chr17-45369617;