5-142770901-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001135608.3(ARHGAP26):​c.140T>C​(p.Ile47Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,608,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000014 ( 0 hom. )

Consequence

ARHGAP26
NM_001135608.3 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06

Publications

0 publications found
Variant links:
Genes affected
ARHGAP26 (HGNC:17073): (Rho GTPase activating protein 26) Interaction of a cell with the extracellular matrix triggers integrin cell surface receptors to begin signaling cascades that regulate the organization of the actin-cytoskeleton. One of the proteins involved in these cascades is focal adhesion kinase. The protein encoded by this gene is a GTPase activating protein that binds to focal adhesion kinase and mediates the activity of the GTP binding proteins RhoA and Cdc42. Defects in this gene are a cause of juvenile myelomonocytic leukemia (JMML). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]
ARHGAP26 Gene-Disease associations (from GenCC):
  • juvenile myelomonocytic leukemia
    Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.4156566).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGAP26NM_001135608.3 linkc.140T>C p.Ile47Thr missense_variant Exon 1 of 23 ENST00000645722.2 NP_001129080.1 Q9UNA1-2A0A0S2Z536

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGAP26ENST00000645722.2 linkc.140T>C p.Ile47Thr missense_variant Exon 1 of 23 NM_001135608.3 ENSP00000495131.1 Q9UNA1-2
ARHGAP26ENST00000274498.9 linkc.140T>C p.Ile47Thr missense_variant Exon 1 of 23 1 ENSP00000274498.4 Q9UNA1-1
ARHGAP26ENST00000642734.1 linkc.-429T>C upstream_gene_variant ENSP00000495827.1 A0A2R8YGB3

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152082
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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:
0.0000122
AC:
3
AN:
245912
AF XY:
0.00000750
show subpopulations
Gnomad AFR exome
AF:
0.000191
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS 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:
0.00000137
AC:
2
AN:
1456548
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
724744
show subpopulations
African (AFR)
AF:
0.0000303
AC:
1
AN:
33048
American (AMR)
AF:
0.00
AC:
0
AN:
44304
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25968
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38962
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85838
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53244
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5746
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1109298
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60140
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152082
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74280
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41432
American (AMR)
AF:
0.00
AC:
0
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5156
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67990
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 08, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.140T>C (p.I47T) alteration is located in exon 1 (coding exon 1) of the ARHGAP26 gene. This alteration results from a T to C substitution at nucleotide position 140, causing the isoleucine (I) at amino acid position 47 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
Pathogenic
0.66
BayesDel_addAF
Uncertain
0.015
T
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T;.;T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.76
.;T;T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.42
T;T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
2.0
M;M;M
PhyloP100
6.1
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-3.2
D;.;D
REVEL
Uncertain
0.32
Sift
Uncertain
0.0010
D;.;D
Sift4G
Uncertain
0.0020
D;.;D
Polyphen
0.88
P;P;P
Vest4
0.55
MVP
0.35
MPC
1.2
ClinPred
0.99
D
GERP RS
5.7
PromoterAI
0.019
Neutral
Varity_R
0.50
gMVP
0.61
Mutation Taster
=55/45
polymorphism

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

Other links and lift over

dbSNP: rs147221601; hg19: chr5-142150466; API