chr5-141659473-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_022481.6(ARAP3):c.3271G>A(p.Asp1091Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000224 in 1,614,032 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 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )
Consequence
ARAP3
NM_022481.6 missense
NM_022481.6 missense
Scores
2
5
10
Clinical Significance
Conservation
PhyloP100: 7.16
Genes affected
ARAP3 (HGNC:24097): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3) This gene encodes a phosphoinositide binding protein containing ARF-GAP, RHO-GAP, RAS-associating, and pleckstrin homology domains. The ARF-GAP and RHO-GAP domains cooperate in mediating rearrangements in the cell cytoskeleton and cell shape. It is a specific PtdIns(3,4,5)P3/PtdIns(3,4)P2-stimulated Arf6-GAP protein. An alternatively spliced transcript has been found for this gene, but its biological validity has not been determined. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.24313346).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARAP3 | NM_022481.6 | c.3271G>A | p.Asp1091Asn | missense_variant | 23/33 | ENST00000239440.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARAP3 | ENST00000239440.9 | c.3271G>A | p.Asp1091Asn | missense_variant | 23/33 | 1 | NM_022481.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000197 AC: 30AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000219 AC: 55AN: 251474Hom.: 0 AF XY: 0.000235 AC XY: 32AN XY: 135912
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GnomAD4 exome AF: 0.000227 AC: 332AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.000234 AC XY: 170AN XY: 727228
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GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74338
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 16, 2022 | The c.3271G>A (p.D1091N) alteration is located in exon 23 (coding exon 22) of the ARAP3 gene. This alteration results from a G to A substitution at nucleotide position 3271, causing the aspartic acid (D) at amino acid position 1091 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.;D
REVEL
Benign
Sift
Benign
T;T;.;T
Sift4G
Uncertain
D;T;D;T
Polyphen
D;D;D;.
Vest4
MVP
MPC
1.0
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at