13-101567725-T-C

Position:

• chr13-101567725-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_004791.3(ITGBL1):​c.343T>C​(p.Cys115Arg) variant causes a missense change. 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: 32)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.16

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.986

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.343T>C	p.Cys115Arg	missense_variant	3/11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271756.2	c.64T>C	p.Cys22Arg	missense_variant	2/10		NP_001258685.1
ITGBL1	NM_001271754.2	c.-81T>C		5_prime_UTR_variant	2/11		NP_001258683.1
ITGBL1	NM_001271755.2	c.317-7699T>C		intron_variant			NP_001258684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.343T>C	p.Cys115Arg	missense_variant	3/11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.317-7699T>C		intron_variant		1		ENSP00000481484.1
ITGBL1	ENST00000376162.7	c.64T>C	p.Cys22Arg	missense_variant	2/10	2		ENSP00000365332.3
ITGBL1	ENST00000545560.6	c.-81T>C		5_prime_UTR_variant	2/11	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Sep 30, 2024

The c.343T>C (p.C115R) alteration is located in exon 3 (coding exon 3) of the ITGBL1 gene. This alteration results from a T to C substitution at nucleotide position 343, causing the cysteine (C) at amino acid position 115 to be replaced by an arginine (R). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T;.
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;T;D
M_CAP	Pathogenic	0.87	D
MetaRNN	Pathogenic	0.99	D;D;D
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Pathogenic	4.3	H;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-7.3	D;.;D
REVEL	Pathogenic	0.96
Sift	Uncertain	0.0010	D;.;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.99
MutPred		0.80		Gain of catalytic residue at K114 (P = 0);.;.;
MVP		0.91
MPC		1.1
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.96
gMVP		0.99

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: chr13-102220076;