11-6478129-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001376558.2(ARFIP2):c.607G>A(p.Val203Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,936 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 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
ARFIP2
NM_001376558.2 missense
NM_001376558.2 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 3.72
Genes affected
ARFIP2 (HGNC:17160): (ADP ribosylation factor interacting protein 2) Enables several functions, including GTP-dependent protein binding activity; membrane curvature sensor activity; and phosphatidylinositol-4-phosphate binding activity. Involved in actin cytoskeleton organization. Located in cell cortex; ruffle; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.386818).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARFIP2 | NM_001376558.2 | c.607G>A | p.Val203Met | missense_variant | 6/8 | ENST00000396777.8 | NP_001363487.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152076Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251474Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135908
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461860Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3AN XY: 727238
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152076Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74292
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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 | Nov 23, 2021 | The c.706G>A (p.V236M) alteration is located in exon 6 (coding exon 5) of the ARFIP2 gene. This alteration results from a G to A substitution at nucleotide position 706, causing the valine (V) at amino acid position 236 to be replaced by a methionine (M). 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
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;L;L;.;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N;N;N;N
REVEL
Uncertain
Sift
Benign
.;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
1.0
.;D;D;.;.
Vest4
MutPred
0.46
.;Gain of MoRF binding (P = 0.4355);Gain of MoRF binding (P = 0.4355);.;.;
MVP
MPC
1.4
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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