chr10-15684035-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The NM_003638.3(ITGA8):​c.537C>A​(p.Ser179Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,614,156 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ITGA8
NM_003638.3 missense

Scores

3
7
9

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.894
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 10-15684035-G-T is Benign according to our data. Variant chr10-15684035-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 522875.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000722 (11/152322) while in subpopulation EAS AF= 0.00135 (7/5182). AF 95% confidence interval is 0.000633. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ITGA8NM_003638.3 linkc.537C>A p.Ser179Arg missense_variant 4/30 ENST00000378076.4 NP_003629.2 P53708B4DN28
ITGA8NM_001291494.2 linkc.537C>A p.Ser179Arg missense_variant 4/29 NP_001278423.1 B4DN28
ITGA8XM_011519752.3 linkc.537C>A p.Ser179Arg missense_variant 4/24 XP_011518054.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ITGA8ENST00000378076.4 linkc.537C>A p.Ser179Arg missense_variant 4/301 NM_003638.3 ENSP00000367316.3 P53708

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00135
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251284
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135798
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000218
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461834
Hom.:
0
Cov.:
30
AF XY:
0.0000124
AC XY:
9
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000722
AC:
11
AN:
152322
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00135
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000125
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Renal hypodysplasia/aplasia 1 Benign:1
Likely benign, criteria provided, single submitterclinical testingGenomic Research Center, Shahid Beheshti University of Medical SciencesMay 03, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.77
BayesDel_addAF
Benign
-0.019
T
BayesDel_noAF
Uncertain
0.0
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.28
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.91
D
M_CAP
Pathogenic
0.43
D
MetaRNN
Uncertain
0.73
D
MetaSVM
Uncertain
-0.18
T
MutationAssessor
Benign
1.6
L
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-1.9
N
REVEL
Uncertain
0.57
Sift
Benign
0.082
T
Sift4G
Benign
0.26
T
Polyphen
1.0
D
Vest4
0.69
MutPred
0.33
Gain of methylation at S179 (P = 0.0367);
MVP
0.84
MPC
0.44
ClinPred
0.94
D
GERP RS
-3.4
Varity_R
0.20
gMVP
0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748467820; hg19: chr10-15726034; API