17-50056465-C-T

Variant names:

• chr17-50056465-C-T
• rs1907815596
• NM_002204.4:c.26C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002204.4(ITGA3):​c.26C>T​(p.Pro9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,385,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: ITGA3 NM_002204.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.409
• Publications: 0 publications found

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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp, ClinGen

ACMG classification

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=0.2286663).

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.26C>T	p.Pro9Leu	missense	Exon 1 of 26	NP_002195.1	P26006-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA3	ENST00000320031.13	TSL:1 MANE Select	c.26C>T	p.Pro9Leu	missense	Exon 1 of 26	ENSP00000315190.8	P26006-2
	ITGA3	ENST00000007722.11	TSL:5	c.26C>T	p.Pro9Leu	missense	Exon 1 of 25	ENSP00000007722.7	P26006-1
	ITGA3	ENST00000876971.1		c.26C>T	p.Pro9Leu	missense	Exon 2 of 27	ENSP00000547030.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1385700 Hom.: 0 Cov.: 31 AF XY: 0.00000439 AC XY: 3 AN XY: 682830

African (AFR) AF: 0.00 AC: 0 AN: 30004

American (AMR) AF: 0.00 AC: 0 AN: 34922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24776

East Asian (EAS) AF: 0.0000581 AC: 2 AN: 34436

South Asian (SAS) AF: 0.00 AC: 0 AN: 77948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4590

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1074064

Other (OTH) AF: 0.00 AC: 0 AN: 57352

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.41
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.29
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.0	B
Vest4		0.12
MutPred		0.34		Gain of helix (P = 0.0164)
MVP		0.77
MPC		0.38
ClinPred		0.71	D
GERP RS		5.3
PromoterAI		0.033	Neutral
Varity_R		0.043
gMVP		0.33

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

Other links and lift over

dbSNP: rs1907815596; hg19: chr17-48133829;