rs1368499306

Variant names:

• chr17-50056516-G-A
• rs1368499306
• NM_002204.4:c.77G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-50056516-G-A
• chr17-50056516-G-C

Variant summary

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

The NM_002204.4(ITGA3):​c.77G>A​(p.Gly26Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,628 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G26A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ITGA3 NM_002204.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.77G>A	p.Gly26Asp	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.77G>A	p.Gly26Asp	missense	Exon 1 of 26	ENSP00000315190.8	P26006-2
	ITGA3	ENST00000007722.11	TSL:5	c.77G>A	p.Gly26Asp	missense	Exon 1 of 25	ENSP00000007722.7	P26006-1
	ITGA3	ENST00000876971.1		c.77G>A	p.Gly26Asp	missense	Exon 2 of 27	ENSP00000547030.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 148874 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398628 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689950

African (AFR) AF: 0.00 AC: 0 AN: 31622

American (AMR) AF: 0.00 AC: 0 AN: 35768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35758

South Asian (SAS) AF: 0.00 AC: 0 AN: 79298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5538

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079580

Other (OTH) AF: 0.00 AC: 0 AN: 57976

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.069
Eigen_PC	Benign	0.079
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.7
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.77	N
REVEL	Uncertain	0.36
Sift	Benign	0.23	T
Sift4G	Benign	0.15	T
Polyphen		0.23	B
Vest4		0.58
MutPred		0.53		Loss of helix (P = 0.1299)
MVP		0.76
MPC		0.49
ClinPred		0.65	D
GERP RS		5.3
PromoterAI		-0.025	Neutral
Varity_R		0.16
gMVP		0.39
Mutation Taster		=92/8	polymorphism

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: rs1368499306; hg19: chr17-48133880;