12-54403647-C-A

Position:

• chr12-54403647-C-A

Variant summary

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

The NM_002205.5(ITGA5):​c.1754G>T​(p.Arg585Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGA5 NM_002205.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769

Genes affected

ITGA5 (HGNC:6141): (integrin subunit alpha 5) The product of this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha subunit and a beta subunit that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 5 subunit. This subunit associates with the beta 1 subunit to form a fibronectin receptor. This integrin may promote tumor invasion, and higher expression of this gene may be correlated with shorter survival time in lung cancer patients. Note that the integrin alpha 5 and integrin alpha V subunits are encoded by distinct genes. [provided by RefSeq, Oct 2015]

ITGA5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA5	NM_002205.5	c.1754G>T	p.Arg585Ile	missense_variant	17/30	ENST00000293379.9	NP_002196.4
ITGA5	XM_024448970.2	c.242G>T	p.Arg81Ile	missense_variant	4/17		XP_024304738.1
GPR84-AS1	NR_120486.1	n.207-3750C>A		intron_variant
GPR84-AS1	NR_120487.1	n.207-3750C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA5	ENST00000293379.9	c.1754G>T	p.Arg585Ile	missense_variant	17/30	1	NM_002205.5	ENSP00000293379.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000235 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.073
Eigen_PC	Benign	-0.073
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.88	T
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.10
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.054	T
Polyphen		0.57	P
Vest4		0.54
MutPred		0.30		Loss of disorder (P = 0.1092);
MVP		0.66
MPC		1.3
ClinPred		0.98	D
GERP RS		3.3
Varity_R		0.56
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

LitVar

Other links and lift over

dbSNP: rs12318746; hg19: chr12-54797431;