Genetic Variant NM_001004439.2:c.3336G>C (chr15-68307393-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004439.2(ITGA11):c.3336G>C(p.Gln1112His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.247

Variant links:

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]

ITGA11 links:

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ACMG classification

Classification was made for transcript

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=0.16825446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA11	NM_001004439.2 link	c.3336G>C	p.Gln1112His	missense_variant	Exon 28 of 30	ENST00000315757.9	NP_001004439.1	Q9UKX5-1B3KTN6
ITGA11	XM_011521363.3 link	c.3129G>C	p.Gln1043His	missense_variant	Exon 26 of 28		XP_011519665.1
ITGA11	XM_005254228.4 link	c.3030G>C	p.Gln1010His	missense_variant	Exon 26 of 28		XP_005254285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA11	ENST00000315757.9 link	c.3336G>C	p.Gln1112His	missense_variant	Exon 28 of 30	1	NM_001004439.2	ENSP00000327290.7		Q9UKX5-1
ITGA11	ENST00000423218.6 link	c.3339G>C	p.Gln1113His	missense_variant	Exon 28 of 30	2		ENSP00000403392.2		Q9UKX5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 15, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3336G>C (p.Q1112H) alteration is located in exon 28 (coding exon 28) of the ITGA11 gene. This alteration results from a G to C substitution at nucleotide position 3336, causing the glutamine (Q) at amino acid position 1112 to be replaced by a histidine (H). 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

0.17

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.056

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;L

PhyloP100

0.25

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.062

Sift

Benign

0.062

T;T

Sift4G

Benign

0.062

T;T

Polyphen

0.0040

.;B

Vest4

0.12

MutPred

0.40

.;Gain of sheet (P = 0.0344);

MVP

0.69

MPC

0.10

ClinPred

0.49

GERP RS

4.7

Varity_R

0.15

gMVP

0.59

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

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