rs757047260

Variant names:

• chr15-68303812-C-A
• rs757047260
• NM_001004439.2:c.3455G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-68303812-C-A
• chr15-68303812-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001004439.2(ITGA11):​c.3455G>T​(p.Gly1152Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. G1152D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGA11 NM_001004439.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.99
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.887

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.3455G>T	p.Gly1152Val	missense	Exon 29 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.3455G>T	p.Gly1152Val	missense	Exon 29 of 30	ENSP00000327290.7	Q9UKX5-1
	ITGA11	ENST00000423218.6	TSL:2	c.3458G>T	p.Gly1153Val	missense	Exon 29 of 30	ENSP00000403392.2	Q9UKX5-2
	ITGA11	ENST00000902076.1		c.3407G>T	p.Gly1136Val	missense	Exon 29 of 30	ENSP00000572135.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 247590 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.84	D
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		7.0
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-8.5	D
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.46		Gain of helix (P = 0.2059)
MVP		0.88
MPC		0.60
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.97
gMVP		0.89
Mutation Taster		=18/82	disease causing

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: rs757047260; hg19: chr15-68596150;