dbSNP rs908827953: ITGA3:p.Val30Ile (chr17-50056527-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002204.4(ITGA3):c.88G>A(p.Val30Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V30L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ITGA3
NM_002204.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.19

Publications

0 publications found

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]

ITGA3 Gene-Disease associations (from GenCC):

epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, PanelApp Australia, Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ITGA3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.256122).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002204.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA3	NM_002204.4	MANE Select	c.88G>A	p.Val30Ile	missense	Exon 1 of 26	NP_002195.1	P26006-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA3	ENST00000320031.13	TSL:1 MANE Select	c.88G>A	p.Val30Ile	missense	Exon 1 of 26	ENSP00000315190.8	P26006-2
ITGA3	ENST00000007722.11	TSL:5	c.88G>A	p.Val30Ile	missense	Exon 1 of 25	ENSP00000007722.7	P26006-1
ITGA3	ENST00000876971.1		c.88G>A	p.Val30Ile	missense	Exon 2 of 27	ENSP00000547030.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1400904

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691358

African (AFR)

AF:

0.00

AC:

AN:

31696

American (AMR)

AF:

0.00

AC:

AN:

35954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25188

East Asian (EAS)

AF:

0.00

AC:

AN:

35890

South Asian (SAS)

AF:

0.00

AC:

AN:

79456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48036

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1081008

Other (OTH)

AF:

0.00

AC:

AN:

58080

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000330

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

-0.12

Eigen_PC

Benign

0.095

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.26

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.0

PhyloP100

3.2

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.14

REVEL

Uncertain

0.32

Sift

Benign

0.19

Sift4G

Benign

0.36

Polyphen

0.082

Vest4

0.058

MutPred

0.48

Gain of catalytic residue at L35 (P = 0.1003)

MVP

0.77

MPC

0.33

ClinPred

0.68

GERP RS

5.3

PromoterAI

0.31

Neutral

(source)

Varity_R

0.098

gMVP

0.10

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over