3-124773748-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002213.5(ITGB5):​c.1858G>A​(p.Ala620Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,492 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ITGB5
NM_002213.5 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56
Variant links:
Genes affected
ITGB5 (HGNC:6160): (integrin subunit beta 5) This gene encodes a beta subunit of integrin, which can combine with different alpha chains to form a variety of integrin heterodimers. Integrins are integral cell-surface receptors that participate in cell adhesion as well as cell-surface mediated signaling. The alphav beta5 integrin is involved in adhesion to vitronectin. [provided by RefSeq, Aug 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITGB5NM_002213.5 linkc.1858G>A p.Ala620Thr missense_variant Exon 11 of 15 ENST00000296181.9 NP_002204.2 P18084L7RT22

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITGB5ENST00000296181.9 linkc.1858G>A p.Ala620Thr missense_variant Exon 11 of 15 1 NM_002213.5 ENSP00000296181.4 P18084
ITGB5ENST00000481591.5 linkc.925G>A p.Ala309Thr missense_variant Exon 5 of 7 5 ENSP00000420814.1 H7C5U2
ITGB5ENST00000461306.1 linkn.197G>A non_coding_transcript_exon_variant Exon 2 of 5 4
ITGB5ENST00000488466.5 linkc.*71G>A downstream_gene_variant 5 ENSP00000477446.1 V9GZ57

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251348
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460492
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
726576
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 23, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1858G>A (p.A620T) alteration is located in exon 11 (coding exon 11) of the ITGB5 gene. This alteration results from a G to A substitution at nucleotide position 1858, causing the alanine (A) at amino acid position 620 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
0.30
BayesDel_addAF
Uncertain
0.021
T
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.34
T
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.56
D
MetaSVM
Uncertain
0.17
D
MutationAssessor
Benign
0.24
N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.9
N
REVEL
Uncertain
0.40
Sift
Benign
0.094
T
Sift4G
Benign
0.38
T
Polyphen
0.76
P
Vest4
0.56
MutPred
0.49
Loss of catalytic residue at A620 (P = 0.0396);
MVP
0.97
MPC
0.53
ClinPred
0.55
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.10
gMVP
0.73

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: rs1243298041; hg19: chr3-124492595; API