13-101579365-T-A

Position:

• chr13-101579365-T-A

Variant summary

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

The NM_004791.3(ITGBL1):​c.665T>A​(p.Ile222Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.61

Genes affected

ITGBL1 (HGNC:6164): (integrin subunit beta like 1) This gene encodes a beta integrin-related protein that is a member of the EGF-like protein family. The encoded protein contains integrin-like cysteine-rich repeats. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

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
ITGBL1	NM_004791.3	c.665T>A	p.Ile222Asn	missense_variant	5/11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.518T>A	p.Ile173Asn	missense_variant	4/10		NP_001258684.1
ITGBL1	NM_001271756.2	c.386T>A	p.Ile129Asn	missense_variant	4/10		NP_001258685.1
ITGBL1	NM_001271754.2	c.242T>A	p.Ile81Asn	missense_variant	4/11		NP_001258683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.665T>A	p.Ile222Asn	missense_variant	5/11	1	NM_004791.3	ENSP00000365351	P1
ITGBL1	ENST00000618057.4	c.518T>A	p.Ile173Asn	missense_variant	4/10	1		ENSP00000481484
ITGBL1	ENST00000376162.7	c.386T>A	p.Ile129Asn	missense_variant	4/10	2		ENSP00000365332
ITGBL1	ENST00000545560.6	c.242T>A	p.Ile81Asn	missense_variant	4/11	2		ENSP00000439903

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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2022

The c.665T>A (p.I222N) alteration is located in exon 5 (coding exon 5) of the ITGBL1 gene. This alteration results from a T to A substitution at nucleotide position 665, causing the isoleucine (I) at amino acid position 222 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;T;T;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.67	D;D;D;D;D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	1.7	.;L;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.010	.;N;.;N;N
REVEL	Pathogenic	0.67
Sift	Uncertain	0.025	.;D;.;D;D
Sift4G	Benign	0.13	T;D;T;T;T
Polyphen		1.0	.;D;.;.;.
Vest4		0.60
MutPred		0.43		.;Gain of catalytic residue at I222 (P = 0.0083);.;.;.;
MVP		0.73
MPC		0.94
ClinPred		0.82	D
GERP RS		5.3
Varity_R		0.32
gMVP		0.70

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: chr13-102231716;