NM_000212.3:c.40G>C

Variant names:

• chr17-47253901-G-C
• NM_000212.3:c.40G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000212.3(ITGB3):​c.40G>C​(p.Val14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000805 in 1,242,410 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: 8.0e-7 (0 hom.)
• Consequence: ITGB3 NM_000212.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05045393).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3	c.40G>C	p.Val14Leu	missense_variant	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.40G>C	p.Val14Leu	missense_variant	Exon 1 of 15	1	NM_000212.3	ENSP00000452786.2
ITGB3	ENST00000571680.1	c.40G>C	p.Val14Leu	missense_variant	Exon 1 of 9	1		ENSP00000461626.1
ENSG00000259753	ENST00000560629.1	n.4G>C		non_coding_transcript_exon_variant	Exon 1 of 18	2		ENSP00000456711.2
ITGB3	ENST00000696963.1	c.40G>C	p.Val14Leu	missense_variant	Exon 1 of 14			ENSP00000513002.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.05e-7 AC: 1 AN: 1242410 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 610550

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: 0.00000100

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	0.090
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.7
DANN	Benign	0.79
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.19	N;.
Sift	Benign	0.76	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.12
MutPred		0.54		Loss of MoRF binding (P = 0.081);Loss of MoRF binding (P = 0.081);
MVP		0.61
MPC		0.40
ClinPred		0.041	T
GERP RS		-2.7
Varity_R		0.046
gMVP		0.53

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: chr17-45331267;