15-68307671-G-A

Variant names:

• chr15-68307671-G-A
• rs1474822857
• NM_001004439.2:c.3200C>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.3200C>T​(p.Ser1067Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGA11 NM_001004439.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.90
• Publications: 1 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, 0.806

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.3200C>T	p.Ser1067Phe	missense	Exon 27 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.3200C>T	p.Ser1067Phe	missense	Exon 27 of 30	ENSP00000327290.7	Q9UKX5-1
	ITGA11	ENST00000423218.6	TSL:2	c.3203C>T	p.Ser1068Phe	missense	Exon 27 of 30	ENSP00000403392.2	Q9UKX5-2
	ITGA11	ENST00000902076.1		c.3152C>T	p.Ser1051Phe	missense	Exon 27 of 30	ENSP00000572135.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.25
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.017	D
Polyphen		0.71	P
Vest4		0.76
MutPred		0.61		Loss of disorder (P = 0.0204)
MVP		0.86
MPC		0.13
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.41
gMVP		0.43

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: rs1474822857; hg19: chr15-68600009;