chr13-101579296-A-G

Position:

• chr13-101579296-A-G

Variant summary

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

The NM_004791.3(ITGBL1):​c.596A>G​(p.Lys199Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,360 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K199N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.87

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	UniProt
ITGBL1	NM_004791.3	c.596A>G	p.Lys199Arg	missense_variant	5/11	ENST00000376180.8
ITGBL1	NM_001271755.2	c.449A>G	p.Lys150Arg	missense_variant	4/10
ITGBL1	NM_001271756.2	c.317A>G	p.Lys106Arg	missense_variant	4/10
ITGBL1	NM_001271754.2	c.173A>G	p.Lys58Arg	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGBL1	ENST00000376180.8	c.596A>G	p.Lys199Arg	missense_variant	5/11	1	NM_004791.3	P1
ITGBL1	ENST00000618057.4	c.449A>G	p.Lys150Arg	missense_variant	4/10	1
ITGBL1	ENST00000376162.7	c.317A>G	p.Lys106Arg	missense_variant	4/10	2
ITGBL1	ENST00000545560.6	c.173A>G	p.Lys58Arg	missense_variant	4/11	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461360 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726980

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

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

Dec 27, 2023

The c.596A>G (p.K199R) alteration is located in exon 5 (coding exon 5) of the ITGBL1 gene. This alteration results from a A to G substitution at nucleotide position 596, causing the lysine (K) at amino acid position 199 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	Benign	0.097
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0068	T;T;T;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.60	T;T;T;D;T
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.45	T;T;T;T;T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	0.93	.;L;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.45	.;N;.;N;N
REVEL	Uncertain	0.59
Sift	Benign	0.054	.;T;.;T;T
Sift4G	Benign	0.35	T;T;T;T;T
Polyphen		0.63	.;P;.;.;.
Vest4		0.49
MutPred		0.48		.;Gain of catalytic residue at N204 (P = 0);.;.;.;
MVP		0.70
MPC		0.57
ClinPred		0.90	D
GERP RS		5.3
Varity_R		0.13
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr13-102231647;