17-50077122-G-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_002204.4(ITGA3):​c.2070+1G>C variant causes a splice donor, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

ITGA3
NM_002204.4 splice_donor, intron

Scores

5
1
1
Splicing: ADA: 1.000
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.18
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 Pathogenic. Variant got 10 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ITGA3NM_002204.4 linkc.2070+1G>C splice_donor_variant, intron_variant ENST00000320031.13 NP_002195.1 P26006-2A0A140VJM0
ITGA3XM_005257308.3 linkc.1665+1G>C splice_donor_variant, intron_variant XP_005257365.1
ITGA3XM_047435922.1 linkc.2070+1G>C splice_donor_variant, intron_variant XP_047291878.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ITGA3ENST00000320031.13 linkc.2070+1G>C splice_donor_variant, intron_variant 1 NM_002204.4 ENSP00000315190.8 P26006-2
ITGA3ENST00000007722.11 linkc.2070+1G>C splice_donor_variant, intron_variant 5 ENSP00000007722.7 P26006-1
ITGA3ENST00000506827.1 linkc.204+1G>C splice_donor_variant, intron_variant 3 ENSP00000426142.1 H0YA49
ITGA3ENST00000505306.5 linkn.2735G>C non_coding_transcript_exon_variant 14/242

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.62
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
35
DANN
Uncertain
0.99
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.87
FATHMM_MKL
Pathogenic
0.98
D
GERP RS
5.3

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.93
SpliceAI score (max)
1.0
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.48
Position offset: -40
DS_DL_spliceai
1.0
Position offset: -1

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: rs797045048; hg19: chr17-48154486; API