chr17-47253863-T-G

Variant names:

• chr17-47253863-T-G
• NM_000212.3:c.2T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_000212.3(ITGB3):​c.2T>G​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000923 in 1,083,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 9.2e-7 (0 hom.)
• Consequence: ITGB3 NM_000212.3 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.577

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 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 48 codons. Genomic position: 47274481. Lost 0.060 part of the original CDS.
• 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.2T>G	p.Met1?	start_lost	Exon 1 of 15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7	c.2T>G	p.Met1?	start_lost	Exon 1 of 15	1	NM_000212.3	ENSP00000452786.2
ITGB3	ENST00000571680.1	c.2T>G	p.Met1?	start_lost	Exon 1 of 9	1		ENSP00000461626.1
ITGB3	ENST00000696963.1	c.2T>G	p.Met1?	start_lost	Exon 1 of 14			ENSP00000513002.1
ENSG00000259753	ENST00000560629.1	n.-35T>G		upstream_gene_variant		2		ENSP00000456711.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.23e-7 AC: 1 AN: 1083546 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 516328

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: 0.00000108

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
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.25
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.28	T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.90	D;D
M_CAP	Pathogenic	0.89	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Benign	-0.92	T
PROVEAN	Benign	0.030	N;.
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.15	T;T
Polyphen		0.032	B;.
Vest4		0.79
MutPred		1.0		Gain of methylation at M1 (P = 0.0051);Gain of methylation at M1 (P = 0.0051);
MVP		0.99
ClinPred		0.99	D
GERP RS		2.1
Varity_R		0.96
gMVP		0.94

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: chr17-45331229;