10-15531057-C-T

Variant names:

Variant summary

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

The NM_003638.3(ITGA8):c.2975G>A(p.Ser992Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 1,505,262 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ITGA8
NM_003638.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.0170

Publications

1 publications found

Variant links:

Genes affected

ITGA8 (HGNC:6144): (integrin subunit alpha 8) Integrins are heterodimeric transmembrane receptor proteins that mediate numerous cellular processes including cell adhesion, cytoskeletal rearrangement, and activation of cell signaling pathways. Integrins are composed of alpha and beta subunits. This gene encodes the alpha 8 subunit of the heterodimeric integrin alpha8beta1 protein. The encoded protein is a single-pass type 1 membrane protein that contains multiple FG-GAP repeats. This repeat is predicted to fold into a beta propeller structure. This gene regulates the recruitment of mesenchymal cells into epithelial structures, mediates cell-cell interactions, and regulates neurite outgrowth of sensory and motor neurons. The integrin alpha8beta1 protein thus plays an important role in wound-healing and organogenesis. Mutations in this gene have been associated with renal hypodysplasia/aplasia-1 (RHDA1) and with several animal models of chronic kidney disease. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2014]

ITGA8 Gene-Disease associations (from GenCC):

renal hypodysplasia/aplasia 1
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
bilateral renal agenesis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ITGA8 links:

Genome browser will be placed here

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=0.08106732).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003638.3. 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
	ITGA8	NM_003638.3	MANE Select	c.2975G>A	p.Ser992Asn	missense	Exon 28 of 30	NP_003629.2	P53708
	ITGA8	NM_001291494.2		c.2930G>A	p.Ser977Asn	missense	Exon 27 of 29	NP_001278423.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA8	ENST00000378076.4	TSL:1 MANE Select	c.2975G>A	p.Ser992Asn	missense	Exon 28 of 30	ENSP00000367316.3	P53708
ITGA8	ENST00000882526.1		c.2881-11645G>A		intron	N/A	ENSP00000552585.1
ITGA8	ENST00000967017.1		c.2836-11645G>A		intron	N/A	ENSP00000637076.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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:

0.0000137

AC:

AN:

218882

AF XY:

0.0000168

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000636

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000192

GnomAD4 exome

AF:

0.0000177

AC:

AN:

1352950

Hom.:

Cov.:

AF XY:

0.0000148

AC XY:

AN XY:

676764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29944

American (AMR)

AF:

0.00

AC:

AN:

35494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24892

East Asian (EAS)

AF:

0.0000526

AC:

AN:

38008

South Asian (SAS)

AF:

0.0000132

AC:

AN:

75478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5586

European-Non Finnish (NFE)

AF:

0.00000193

AC:

AN:

1033806

Other (OTH)

AF:

0.000335

AC:

AN:

56648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.60

M_CAP

Benign

0.015

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

PhyloP100

0.017

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.0

REVEL

Benign

0.074

Sift

Benign

0.12

Sift4G

Benign

0.15

Polyphen

0.0

Vest4

0.063

MutPred

0.36

Loss of glycosylation at S992 (P = 0.0082)

MVP

0.62

MPC

0.065

ClinPred

0.063

GERP RS

2.3

Varity_R

0.079

gMVP

0.47

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over