13-101598189-A-T

Variant names:

• chr13-101598189-A-T
• NM_004791.3:c.905A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004791.3(ITGBL1):​c.905A>T​(p.Lys302Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,466 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.761

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.905A>T	p.Lys302Ile	missense_variant	Exon 7 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.758A>T	p.Lys253Ile	missense_variant	Exon 6 of 10		NP_001258684.1
ITGBL1	NM_001271756.2	c.626A>T	p.Lys209Ile	missense_variant	Exon 6 of 10		NP_001258685.1
ITGBL1	NM_001271754.2	c.482A>T	p.Lys161Ile	missense_variant	Exon 6 of 11		NP_001258683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.905A>T	p.Lys302Ile	missense_variant	Exon 7 of 11	1	NM_004791.3	ENSP00000365351.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461466 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727048

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T;T;T;.;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.76	D;D;D;D;D
MetaSVM	Uncertain	0.62	D
MutationAssessor	Benign	2.0	.;M;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.8	.;D;.;D;D
REVEL	Pathogenic	0.76
Sift	Benign	0.037	.;D;.;T;T
Sift4G	Benign	0.10	T;T;T;T;T
Polyphen		0.92	.;P;.;.;.
Vest4		0.66
MutPred		0.55		.;Gain of catalytic residue at A303 (P = 0);.;.;.;
MVP		0.65
MPC		0.98
ClinPred		0.99	D
GERP RS		1.7
Varity_R		0.33
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr13-102250539;