13-101452840-C-T

Variant names:

• chr13-101452840-C-T
• rs752269800
• NM_004791.3:c.7C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004791.3(ITGBL1):​c.7C>T​(p.Pro3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.124
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.102077425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.7C>T	p.Pro3Ser	missense_variant	Exon 1 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.7C>T	p.Pro3Ser	missense_variant	Exon 1 of 10		NP_001258684.1
ITGBL1	NM_001271754.2	c.-199C>T		5_prime_UTR_variant	Exon 1 of 11		NP_001258683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.7C>T	p.Pro3Ser	missense_variant	Exon 1 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.7C>T	p.Pro3Ser	missense_variant	Exon 1 of 10	1		ENSP00000481484.1
ITGBL1	ENST00000545560.6	c.-199C>T		5_prime_UTR_variant	Exon 1 of 11	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 250890 AF XY: 0.0000147

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461254 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726982

African (AFR) AF: 0.0000896 AC: 3 AN: 33468

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111494

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74336

African (AFR) AF: 0.0000724 AC: 3 AN: 41444

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000225 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.7C>T (p.P3S) alteration is located in exon 1 (coding exon 1) of the ITGBL1 gene. This alteration results from a C to T substitution at nucleotide position 7, causing the proline (P) at amino acid position 3 to be replaced by a serine (S). 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	0.062
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0098	T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.6	.;L
PhyloP100		0.12
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.55	.;N
REVEL	Benign	0.18
Sift	Benign	0.050	.;D
Sift4G	Benign	0.34	T;T
Polyphen		0.049	.;B
Vest4		0.15
MutPred		0.27		Gain of phosphorylation at P3 (P = 0.0362);Gain of phosphorylation at P3 (P = 0.0362);
MVP		0.35
MPC		0.21
ClinPred		0.071	T
GERP RS		3.6
PromoterAI		-0.040	Neutral
Varity_R		0.031
gMVP		0.52
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs752269800; hg19: chr13-102105191;