Variant 13-101579297-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004791.3(ITGBL1):c.597G>T(p.Lys199Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,613,646 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. K199R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ITGBL1
NM_004791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.83

Variant links:

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]

ITGBL1 links:

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ACMG classification

Classification made for transcript

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
ITGBL1	NM_004791.3 linkuse as main transcript	c.597G>T	p.Lys199Asn	missense_variant	5/11	ENST00000376180.8
ITGBL1	NM_001271755.2 linkuse as main transcript	c.450G>T	p.Lys150Asn	missense_variant	4/10
ITGBL1	NM_001271756.2 linkuse as main transcript	c.318G>T	p.Lys106Asn	missense_variant	4/10
ITGBL1	NM_001271754.2 linkuse as main transcript	c.174G>T	p.Lys58Asn	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGBL1	ENST00000376180.8 linkuse as main transcript	c.597G>T	p.Lys199Asn	missense_variant	5/11	1	NM_004791.3	P1	O95965-1
ITGBL1	ENST00000618057.4 linkuse as main transcript	c.450G>T	p.Lys150Asn	missense_variant	4/10	1
ITGBL1	ENST00000376162.7 linkuse as main transcript	c.318G>T	p.Lys106Asn	missense_variant	4/10	2			O95965-3
ITGBL1	ENST00000545560.6 linkuse as main transcript	c.174G>T	p.Lys58Asn	missense_variant	4/11	2			O95965-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251184

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461446

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000254

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.597G>T (p.K199N) alteration is located in exon 5 (coding exon 5) of the ITGBL1 gene. This alteration results from a G to T substitution at nucleotide position 597, causing the lysine (K) at amino acid position 199 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

0.28

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0069

T;T;T;.;.

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.77

T;D;T;D;T

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.58

D;D;D;D;D

MetaSVM

Uncertain

0.79

MutationAssessor

Benign

1.4

.;L;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.31

.;N;.;N;N

REVEL

Uncertain

0.60

Sift

Benign

0.098

.;T;.;T;T

Sift4G

Benign

0.36

T;T;T;T;T

Polyphen

0.78

.;P;.;.;.

Vest4

0.61

MutPred

0.48

.;Gain of catalytic residue at H197 (P = 2e-04);.;.;.;

MVP

0.80

MPC

0.79

ClinPred

0.42

GERP RS

5.3

Varity_R

0.21

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over