15-68307410-C-T

Variant names:

• chr15-68307410-C-T
• rs187377240
• NM_001004439.2:c.3319G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004439.2(ITGA11):​c.3319G>A​(p.Ala1107Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000642 in 1,558,682 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1107V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000068 (1 hom.)
• Consequence: ITGA11 NM_001004439.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.41

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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20846948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA11	NM_001004439.2	c.3319G>A	p.Ala1107Thr	missense_variant	Exon 28 of 30	ENST00000315757.9	NP_001004439.1
ITGA11	XM_011521363.3	c.3112G>A	p.Ala1038Thr	missense_variant	Exon 26 of 28		XP_011519665.1
ITGA11	XM_005254228.4	c.3013G>A	p.Ala1005Thr	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	c.3319G>A	p.Ala1107Thr	missense_variant	Exon 28 of 30	1	NM_001004439.2	ENSP00000327290.7
ITGA11	ENST00000423218.6	c.3322G>A	p.Ala1108Thr	missense_variant	Exon 28 of 30	2		ENSP00000403392.2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152120 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: 0.000964

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000537 AC: 9 AN: 167486 AF XY: 0.0000675

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000507

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000149

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000675 AC: 95 AN: 1406444 Hom.: 1 Cov.: 31 AF XY: 0.0000590 AC XY: 41 AN XY: 694352

African (AFR) AF: 0.00 AC: 0 AN: 31976

American (AMR) AF: 0.00 AC: 0 AN: 36808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25306

East Asian (EAS) AF: 0.00233 AC: 85 AN: 36412

South Asian (SAS) AF: 0.0000501 AC: 4 AN: 79780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000370 AC: 4 AN: 1082404

Other (OTH) AF: 0.0000343 AC: 2 AN: 58362

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74442

African (AFR) AF: 0.00 AC: 0 AN: 41524

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000432 AC: 5

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3319G>A (p.A1107T) alteration is located in exon 28 (coding exon 28) of the ITGA11 gene. This alteration results from a G to A substitution at nucleotide position 3319, causing the alanine (A) at amino acid position 1107 to be replaced by a threonine (T). 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	0.29
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	.;D
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.1	.;M
PhyloP100		4.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.28
Sift	Benign	0.12	T;T
Sift4G	Benign	0.086	T;T
Polyphen		0.99	.;D
Vest4		0.61
MVP		0.82
MPC		0.33
ClinPred		0.21	T
GERP RS		3.8
Varity_R		0.28
gMVP		0.77
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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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Other links and lift over

dbSNP: rs187377240; hg19: chr15-68599748;