15-68303785-A-C

Variant names:

• chr15-68303785-A-C
• rs907414924
• NM_001004439.2:c.3482T>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001004439.2(ITGA11):​c.3482T>G​(p.Leu1161Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,610,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: ITGA11 NM_001004439.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.25

Genes affected

ITGA11 (HGNC:6136): (integrin subunit alpha 11) This gene encodes an alpha integrin. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This protein contains an I domain, is expressed in muscle tissue, dimerizes with beta 1 integrin in vitro, and appears to bind collagen in this form. Therefore, the protein may be involved in attaching muscle tissue to the extracellular matrix. Alternative transcriptional splice variants have been found for this gene, but their biological validity is not determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA11	NM_001004439.2	c.3482T>G	p.Leu1161Arg	missense_variant	Exon 29 of 30	ENST00000315757.9	NP_001004439.1
ITGA11	XM_011521363.3	c.3275T>G	p.Leu1092Arg	missense_variant	Exon 27 of 28		XP_011519665.1
ITGA11	XM_005254228.4	c.3176T>G	p.Leu1059Arg	missense_variant	Exon 27 of 28		XP_005254285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA11	ENST00000315757.9	c.3482T>G	p.Leu1161Arg	missense_variant	Exon 29 of 30	1	NM_001004439.2	ENSP00000327290.7
ITGA11	ENST00000423218.6	c.3485T>G	p.Leu1162Arg	missense_variant	Exon 29 of 30	2		ENSP00000403392.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32

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: 0.0000122 AC: 3 AN: 246880 Hom.: 0 AF XY: 0.00000746 AC XY: 1 AN XY: 134024

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000268

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000213 AC: 31 AN: 1458654 Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13 AN XY: 725746

Gnomad4 AFR exome AF: 0.0000300

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: 0.0000252

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

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: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.0000595

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3482T>G (p.L1161R) alteration is located in exon 29 (coding exon 29) of the ITGA11 gene. This alteration results from a T to G substitution at nucleotide position 3482, causing the leucine (L) at amino acid position 1161 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	0.63
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.76	.;D
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.063	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Pathogenic	3.3	.;M
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	.;D
Vest4		0.88
MutPred		0.71		.;Gain of MoRF binding (P = 0.0065);
MVP		0.93
MPC		0.65
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.92
gMVP		0.91

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

LitVar

Other links and lift over

dbSNP: rs907414924; hg19: chr15-68596123;