17-50056548-A-G

Variant names:

• chr17-50056548-A-G
• NM_002204.4:c.109A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002204.4(ITGA3):​c.109A>G​(p.Thr37Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ITGA3 NM_002204.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32166317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA3	NM_002204.4	c.109A>G	p.Thr37Ala	missense_variant	Exon 1 of 26	ENST00000320031.13	NP_002195.1
ITGA3	XM_005257308.3	c.109A>G	p.Thr37Ala	missense_variant	Exon 1 of 24		XP_005257365.1
ITGA3	XM_047435922.1	c.109A>G	p.Thr37Ala	missense_variant	Exon 1 of 18		XP_047291878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA3	ENST00000320031.13	c.109A>G	p.Thr37Ala	missense_variant	Exon 1 of 26	1	NM_002204.4	ENSP00000315190.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome Uncertain:1

Feb 06, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.81	T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.22
Sift	Benign	0.13	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.53	P;D
Vest4		0.35
MutPred		0.47		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.67
MPC		1.2
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.20
gMVP		0.41

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-48133912;