3-124796662-G-T

Variant names:

• chr3-124796662-G-T
• rs2291088
• NM_002213.5:c.1419C>A
• ITGB5 p.Ser473Arg

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002213.5(ITGB5):​c.1419C>A​(p.Ser473Arg) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITGB5 NM_002213.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• Publications: 17 publications found

Genes affected

ITGB5 (HGNC:6160): (integrin subunit beta 5) This gene encodes a beta subunit of integrin, which can combine with different alpha chains to form a variety of integrin heterodimers. Integrins are integral cell-surface receptors that participate in cell adhesion as well as cell-surface mediated signaling. The alphav beta5 integrin is involved in adhesion to vitronectin. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.863

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002213.5. 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
	ITGB5	NM_002213.5	MANE Select	c.1419C>A	p.Ser473Arg	missense	Exon 10 of 15	NP_002204.2
	ITGB5	NM_001354764.2		c.1095C>A	p.Ser365Arg	missense	Exon 10 of 15	NP_001341693.1
	ITGB5	NM_001354765.1		c.1095C>A	p.Ser365Arg	missense	Exon 10 of 15	NP_001341694.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB5	ENST00000296181.9	TSL:1 MANE Select	c.1419C>A	p.Ser473Arg	missense	Exon 10 of 15	ENSP00000296181.4	P18084
	ITGB5	ENST00000905025.1		c.1641C>A	p.Ser547Arg	missense	Exon 12 of 17	ENSP00000575084.1
	ITGB5	ENST00000965613.1		c.1533C>A	p.Ser511Arg	missense	Exon 12 of 17	ENSP00000635672.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.74	D
Eigen	Benign	0.17
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.62
gMVP		0.90
Mutation Taster		=48/52	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2291088;

hg19: chr3-124515509;

COSMIC: COSV104609662;

COSMIC: COSV104609662;