17-50076635-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002204.4(ITGA3):ā€‹c.1876C>Gā€‹(p.Gln626Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 š‘“: 0.0000034 ( 0 hom. )

Consequence

ITGA3
NM_002204.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24
Variant links:
Genes affected
ITGA3 (HGNC:6139): (integrin subunit alpha 3) The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function as cell surface adhesion molecules. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 3 subunit. This subunit joins with a beta 1 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. Expression of this gene may be correlated with breast cancer metastasis. [provided by RefSeq, Oct 2015]

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ACMG classification

Classification made for transcript

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=0.27957648).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ITGA3NM_002204.4 linkuse as main transcriptc.1876C>G p.Gln626Glu missense_variant 14/26 ENST00000320031.13 NP_002195.1
ITGA3XM_005257308.3 linkuse as main transcriptc.1471C>G p.Gln491Glu missense_variant 12/24 XP_005257365.1
ITGA3XM_047435922.1 linkuse as main transcriptc.1876C>G p.Gln626Glu missense_variant 14/18 XP_047291878.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ITGA3ENST00000320031.13 linkuse as main transcriptc.1876C>G p.Gln626Glu missense_variant 14/261 NM_002204.4 ENSP00000315190 P1P26006-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000808
AC:
2
AN:
247432
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134238
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000181
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461382
Hom.:
0
Cov.:
34
AF XY:
0.00000413
AC XY:
3
AN XY:
726990
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T;.
Eigen
Benign
0.078
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.72
T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.28
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.7
M;M
MutationTaster
Benign
1.0
D;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.14
Sift
Benign
0.067
T;T
Sift4G
Uncertain
0.010
D;D
Polyphen
0.87
P;B
Vest4
0.21
MVP
0.52
MPC
0.41
ClinPred
0.41
T
GERP RS
3.2
Varity_R
0.25
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs758284330; hg19: chr17-48153999; API