17-50056453-C-T

Variant names:

• chr17-50056453-C-T
• NM_002204.4:c.14C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002204.4(ITGA3):​c.14C>T​(p.Pro5Leu) 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. 14/21 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)
• Consequence: ITGA3 NM_002204.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.395

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10462153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA3	NM_002204.4	c.14C>T	p.Pro5Leu	missense_variant	Exon 1 of 26	ENST00000320031.13	NP_002195.1
ITGA3	XM_005257308.3	c.14C>T	p.Pro5Leu	missense_variant	Exon 1 of 24		XP_005257365.1
ITGA3	XM_047435922.1	c.14C>T	p.Pro5Leu	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.14C>T	p.Pro5Leu	missense_variant	Exon 1 of 26	1	NM_002204.4	ENSP00000315190.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

May 23, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.74	T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.30	N;N
REVEL	Benign	0.053
Sift	Benign	0.16	T;T
Sift4G	Benign	0.087	T;T
Polyphen		0.0	B;B
Vest4		0.089
MutPred		0.23		Gain of MoRF binding (P = 0.0106);Gain of MoRF binding (P = 0.0106);
MVP		0.62
MPC		0.38
ClinPred		0.13	T
GERP RS		3.0
Varity_R		0.069
gMVP		0.24

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: chr17-48133817;