17-47283410-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000212.3(ITGB3):ā€‹c.222C>Gā€‹(p.Asn74Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,118 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: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

ITGB3
NM_000212.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0410
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.24587259).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ITGB3NM_000212.3 linkuse as main transcriptc.222C>G p.Asn74Lys missense_variant 3/15 ENST00000559488.7 NP_000203.2 P05106-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ITGB3ENST00000559488.7 linkuse as main transcriptc.222C>G p.Asn74Lys missense_variant 3/151 NM_000212.3 ENSP00000452786.2 P05106-1
ITGB3ENST00000571680.1 linkuse as main transcriptc.222C>G p.Asn74Lys missense_variant 3/91 ENSP00000461626.1 I3L4X8
ENSG00000259753ENST00000560629.1 linkuse as main transcriptn.186C>G non_coding_transcript_exon_variant 3/182 ENSP00000456711.2 H3BM21
ITGB3ENST00000696963.1 linkuse as main transcriptc.222C>G p.Asn74Lys missense_variant 3/14 ENSP00000513002.1 P05106-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152230
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461888
Hom.:
0
Cov.:
33
AF XY:
0.00000550
AC XY:
4
AN XY:
727242
show subpopulations
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:
0.00000629
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 01, 2024The c.222C>G (p.N74K) alteration is located in exon 3 (coding exon 3) of the ITGB3 gene. This alteration results from a C to G substitution at nucleotide position 222, causing the asparagine (N) at amino acid position 74 to be replaced by a lysine (K). 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
0.10
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.78
D;.
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.76
D
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.25
T;T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
0.40
N;.
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.9
N;.
Sift
Uncertain
0.017
D;.
Sift4G
Uncertain
0.030
D;D
Polyphen
0.0010
B;.
Vest4
0.097
MutPred
0.61
Gain of methylation at N74 (P = 0.0039);Gain of methylation at N74 (P = 0.0039);
MVP
0.88
MPC
0.47
ClinPred
0.84
D
GERP RS
2.3
Varity_R
0.54
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1567764020; hg19: chr17-45360776; COSMIC: COSV71384161; COSMIC: COSV71384161; API