17-47253896-C-A

Position:

• chr17-47253896-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000212.3(ITGB3):​c.35C>A​(p.Ala12Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000168 in 1,192,242 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: ITGB3 NM_000212.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.630

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB3	NM_000212.3	c.35C>A	p.Ala12Glu	missense_variant	1/15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7	c.35C>A	p.Ala12Glu	missense_variant	1/15	1	NM_000212.3	ENSP00000452786	P1
ITGB3	ENST00000571680.1	c.35C>A	p.Ala12Glu	missense_variant	1/9	1		ENSP00000461626
ITGB3	ENST00000696963.1	c.35C>A	p.Ala12Glu	missense_variant	1/14			ENSP00000513002

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000168 AC: 2 AN: 1192242 Hom.: 0 Cov.: 30 AF XY: 0.00000344 AC XY: 2 AN XY: 581804

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000205

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.35C>A (p.A12E) alteration is located in exon 1 (coding exon 1) of the ITGB3 gene. This alteration results from a C to A substitution at nucleotide position 35, causing the alanine (A) at amino acid position 12 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Uncertain	0.48	T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.46	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.1	N;.
Sift	Benign	0.15	T;.
Sift4G	Benign	0.75	T;T
Polyphen		0.078	B;.
Vest4		0.52
MutPred		0.55		Loss of MoRF binding (P = 0.0453);Loss of MoRF binding (P = 0.0453);
MVP		0.93
MPC		0.49
ClinPred		0.11	T
GERP RS		2.1
Varity_R		0.18
gMVP		0.82

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: chr17-45331262;