chr17-50056527-G-C

Variant names:

• chr17-50056527-G-C
• rs908827953
• NM_002204.4:c.88G>C

Variant summary

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

The NM_002204.4(ITGA3):​c.88G>C​(p.Val30Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,400,904 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: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ITGA3 NM_002204.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28430587).

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>C	p.Val30Leu	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.88G>C	p.Val30Leu	missense	Exon 1 of 26	ENSP00000315190.8	P26006-2
	ITGA3	ENST00000007722.11	TSL:5	c.88G>C	p.Val30Leu	missense	Exon 1 of 25	ENSP00000007722.7	P26006-1
	ITGA3	ENST00000876971.1		c.88G>C	p.Val30Leu	missense	Exon 2 of 27	ENSP00000547030.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000131 AC: 2 AN: 152930 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000805

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: 0.00000286 AC: 4 AN: 1400904 Hom.: 0 Cov.: 31 AF XY: 0.00000289 AC XY: 2 AN XY: 691358

African (AFR) AF: 0.00 AC: 0 AN: 31696

American (AMR) AF: 0.0000834 AC: 3 AN: 35954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25188

East Asian (EAS) AF: 0.00 AC: 0 AN: 35890

South Asian (SAS) AF: 0.00 AC: 0 AN: 79456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5596

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1081008

Other (OTH) AF: 0.00 AC: 0 AN: 58080

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.022
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	0.046	D
MutationAssessor	Benign	1.0	L
PhyloP100		3.2
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.29	N
REVEL	Uncertain	0.35
Sift	Benign	0.058	T
Sift4G	Benign	0.16	T
Polyphen		0.0090	B
Vest4		0.10
MutPred		0.49		Loss of catalytic residue at V30 (P = 0.0323)
MVP		0.87
MPC		0.40
ClinPred		0.27	T
GERP RS		5.3
PromoterAI		-0.060	Neutral
Varity_R		0.14
gMVP		0.19

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: rs908827953; hg19: chr17-48133891;