11-72688534-G-A

Variant summary

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

The NM_001040118.3(ARAP1):​c.3991C>T​(p.His1331Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ARAP1
NM_001040118.3 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28816855).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARAP1NM_001040118.3 linkc.3991C>T p.His1331Tyr missense_variant Exon 31 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.3991C>T p.His1331Tyr missense_variant Exon 31 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
May 18, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.3991C>T (p.H1331Y) alteration is located in exon 31 (coding exon 29) of the ARAP1 gene. This alteration results from a C to T substitution at nucleotide position 3991, causing the histidine (H) at amino acid position 1331 to be replaced by a tyrosine (Y). 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
0.20
BayesDel_addAF
Uncertain
0.048
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.031
.;T;.;.;T;T;.;T
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.84
T;T;T;T;T;T;T;T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.29
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.32
T
MutationAssessor
Benign
1.7
.;.;.;.;L;.;.;.
PhyloP100
2.3
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-2.5
D;.;N;N;N;N;D;D
REVEL
Benign
0.23
Sift
Benign
0.70
T;.;T;T;T;T;T;T
Sift4G
Uncertain
0.0080
D;D;D;D;D;T;T;D
Polyphen
0.98
D;.;D;.;D;D;.;.
Vest4
0.38
MutPred
0.47
.;.;.;.;Gain of phosphorylation at H1331 (P = 0.0189);.;.;.;
MVP
0.61
MPC
1.1
ClinPred
0.97
D
GERP RS
5.1
PromoterAI
0.0097
Neutral
Varity_R
0.16
gMVP
0.30
Mutation Taster
=88/12
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: chr11-72399579; API