chr17-47284578-C-T

Variant names:

• chr17-47284578-C-T
• rs74708909
• NM_000212.3:c.497C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_000212.3(ITGB3):​c.497C>T​(p.Thr166Ile) variant causes a missense 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGB3 NM_000212.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a domain VWFA (size 242) in uniprot entity ITB3_HUMAN there are 9 pathogenic changes around while only 1 benign (90%) in NM_000212.3
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3	c.497C>T	p.Thr166Ile	missense_variant	Exon 4 of 15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7	c.497C>T	p.Thr166Ile	missense_variant	Exon 4 of 15	1	NM_000212.3	ENSP00000452786.2
ITGB3	ENST00000571680.1	c.497C>T	p.Thr166Ile	missense_variant	Exon 4 of 9	1		ENSP00000461626.1
ENSG00000259753	ENST00000560629.1	n.461C>T		non_coding_transcript_exon_variant	Exon 4 of 18	2		ENSP00000456711.2
ITGB3	ENST00000696963.1	c.497C>T	p.Thr166Ile	missense_variant	Exon 4 of 14			ENSP00000513002.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Pathogenic	0.80	D;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.31	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	0.90	L;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.8	N;.
Sift	Benign	0.066	T;.
Sift4G	Benign	0.064	T;T
Polyphen		0.0060	B;.
Vest4		0.41
MutPred		0.80		Loss of disorder (P = 0.0626);Loss of disorder (P = 0.0626);
MVP		0.89
MPC		0.49
ClinPred		0.074	T
GERP RS		2.8
Varity_R		0.22
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs74708909; hg19: chr17-45361944;