NM_002204.4:c.1876C>G

Variant names:

• chr17-50076635-C-G
• rs758284330
• NM_002204.4:c.1876C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002204.4(ITGA3):​c.1876C>G​(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. 14/22 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 𝑓: 0.0000034 (0 hom.)
• Consequence: ITGA3 NM_002204.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, Ambry Genetics, Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27957648).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA3	NM_002204.4	MANE Select	c.1876C>G	p.Gln626Glu	missense	Exon 14 of 26	NP_002195.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA3	ENST00000320031.13	TSL:1 MANE Select	c.1876C>G	p.Gln626Glu	missense	Exon 14 of 26	ENSP00000315190.8
	ITGA3	ENST00000007722.11	TSL:5	c.1876C>G	p.Gln626Glu	missense	Exon 14 of 25	ENSP00000007722.7
	ITGA3	ENST00000506827.1	TSL:3	c.10C>G	p.Gln4Glu	missense	Exon 1 of 7	ENSP00000426142.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000808 AC: 2 AN: 247432 AF XY: 0.0000149

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111912

Other (OTH) AF: 0.00 AC: 0 AN: 60384

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 v4.9

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
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.2
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Benign	0.067	T
Sift4G	Uncertain	0.010	D
Polyphen		0.87	P
Vest4		0.21
MVP		0.52
MPC		0.41
ClinPred		0.41	T
GERP RS		3.2
PromoterAI		0.0076	Neutral
Varity_R		0.25
gMVP		0.69
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs758284330; hg19: chr17-48153999;