11-72693723-G-C

Variant summary

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

The NM_001040118.3(ARAP1):​c.3777C>G​(p.His1259Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

ARAP1
NM_001040118.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.150

Publications

0 publications found
Variant links:
Genes affected
ARAP1 (HGNC:16925): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1) The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]
ARAP1-AS1 (HGNC:39993): (ARAP1 antisense RNA 1)

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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=0.07108253).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARAP1NM_001040118.3 linkc.3777C>G p.His1259Gln missense_variant Exon 28 of 35 ENST00000393609.8 NP_001035207.1 Q96P48-6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARAP1ENST00000393609.8 linkc.3777C>G p.His1259Gln missense_variant Exon 28 of 35 2 NM_001040118.3 ENSP00000377233.3 Q96P48-6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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
Apr 04, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.3777C>G (p.H1259Q) alteration is located in exon 28 (coding exon 26) of the ARAP1 gene. This alteration results from a C to G substitution at nucleotide position 3777, causing the histidine (H) at amino acid position 1259 to be replaced by a glutamine (Q). 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
0.17
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
15
DANN
Benign
0.79
DEOGEN2
Benign
0.020
.;T;.;.;T;T;.;T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.78
T;T;T;T;T;T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.071
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.49
N;.;.;.;N;.;.;.
PhyloP100
0.15
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-2.2
N;.;N;N;N;N;N;N
REVEL
Benign
0.023
Sift
Benign
0.29
T;.;T;T;T;T;T;T
Sift4G
Benign
0.14
T;T;T;T;T;T;T;T
Polyphen
0.0010
B;.;B;.;B;B;.;.
Vest4
0.21
MutPred
0.42
Loss of loop (P = 0.0235);.;.;.;Loss of loop (P = 0.0235);.;.;.;
MVP
0.085
MPC
0.33
ClinPred
0.046
T
GERP RS
0.56
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.060
gMVP
0.54
Mutation Taster
=81/19
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

hg19: chr11-72404768; API