17-47292251-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000212.3(ITGB3):​c.1373A>T​(p.Asp458Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITGB3 NM_000212.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39373913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3	c.1373A>T	p.Asp458Val	missense_variant	Exon 10 of 15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7	c.1373A>T	p.Asp458Val	missense_variant	Exon 10 of 15	1	NM_000212.3	ENSP00000452786.2
ENSG00000259753	ENST00000560629.1	n.1337A>T		non_coding_transcript_exon_variant	Exon 10 of 18	2		ENSP00000456711.2
ITGB3	ENST00000696963.1	c.1373A>T	p.Asp458Val	missense_variant	Exon 10 of 14			ENSP00000513002.1
ITGB3	ENST00000573377.1	n.*380A>T		downstream_gene_variant		1		ENSP00000465586.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.76	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.44	N
Sift	Benign	0.28	T
Sift4G	Benign	0.29	T
Polyphen		0.30	B
Vest4		0.33
MutPred		0.56		Loss of catalytic residue at D458 (P = 0.154);
MVP		0.67
MPC		0.68
ClinPred		0.34	T
GERP RS		5.4
Varity_R		0.20
gMVP		0.61

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: chr17-45369617;