rs1000803746

Variant names:

• chr17-50056468-G-A
• rs1000803746
• NM_002204.4:c.29G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-50056468-G-A
• chr17-50056468-G-C

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.29G>A​(p.Arg10His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,384,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ITGA3 NM_002204.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.565
• 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: ClinGen, PanelApp Australia, Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

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=0.1285727).

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.29G>A	p.Arg10His	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.29G>A	p.Arg10His	missense	Exon 1 of 26	ENSP00000315190.8	P26006-2
	ITGA3	ENST00000007722.11	TSL:5	c.29G>A	p.Arg10His	missense	Exon 1 of 25	ENSP00000007722.7	P26006-1
	ITGA3	ENST00000876971.1		c.29G>A	p.Arg10His	missense	Exon 2 of 27	ENSP00000547030.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000289 AC: 4 AN: 1384872 Hom.: 0 Cov.: 31 AF XY: 0.00000440 AC XY: 3 AN XY: 682416

African (AFR) AF: 0.00 AC: 0 AN: 29922

American (AMR) AF: 0.00 AC: 0 AN: 34768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24752

East Asian (EAS) AF: 0.00 AC: 0 AN: 34364

South Asian (SAS) AF: 0.00 AC: 0 AN: 77864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47610

Middle Eastern (MID) AF: 0.000433 AC: 2 AN: 4620

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1073646

Other (OTH) AF: 0.00 AC: 0 AN: 57326

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.56
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.18
Sift	Benign	0.15	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.087
MutPred		0.36		Gain of helix (P = 0.062)
MVP		0.59
MPC		0.46
ClinPred		0.082	T
GERP RS		1.0
PromoterAI		-0.027	Neutral
Varity_R		0.032
gMVP		0.34

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: rs1000803746; hg19: chr17-48133832;