rs761739603

Variant names:

• chr15-68307352-C-A
• rs761739603
• NM_001004439.2:c.3377G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-68307352-C-A
• chr15-68307352-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001004439.2(ITGA11):​c.3377G>T​(p.Arg1126Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,401,842 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1126H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ITGA11 NM_001004439.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.02
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004439.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA11	NM_001004439.2	MANE Select	c.3377G>T	p.Arg1126Leu	missense	Exon 28 of 30	NP_001004439.1	Q9UKX5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA11	ENST00000315757.9	TSL:1 MANE Select	c.3377G>T	p.Arg1126Leu	missense	Exon 28 of 30	ENSP00000327290.7	Q9UKX5-1
	ITGA11	ENST00000423218.6	TSL:2	c.3380G>T	p.Arg1127Leu	missense	Exon 28 of 30	ENSP00000403392.2	Q9UKX5-2
	ITGA11	ENST00000902076.1		c.3329G>T	p.Arg1110Leu	missense	Exon 28 of 30	ENSP00000572135.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1401842 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 691846

African (AFR) AF: 0.00 AC: 0 AN: 31754

American (AMR) AF: 0.00 AC: 0 AN: 36304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25264

East Asian (EAS) AF: 0.00 AC: 0 AN: 36070

South Asian (SAS) AF: 0.00 AC: 0 AN: 79448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5596

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1079880

Other (OTH) AF: 0.00 AC: 0 AN: 58140

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.0
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.25
Sift	Benign	0.10	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.80
MutPred		0.48		Loss of disorder (P = 0.0315)
MVP		0.76
MPC		0.56
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.35
gMVP		0.88
Mutation Taster		=60/40	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: rs761739603; hg19: chr15-68599690;