chr22-42817834-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_014570.5(ARFGAP3):āc.836A>Gā(p.Tyr279Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000559 in 1,610,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
ARFGAP3
NM_014570.5 missense
NM_014570.5 missense
Scores
5
9
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.49
Genes affected
ARFGAP3 (HGNC:661): (ADP ribosylation factor GTPase activating protein 3) The protein encoded by this gene is a GTPase-activating protein (GAP) that associates with the Golgi apparatus and regulates the early secretory pathway of proteins. The encoded protein promotes hydrolysis of ADP-ribosylation factor 1 (ARF1)-bound GTP, which is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is a prerequisite for the fusion of these vesicles with target compartments. The activity of this protein is sensitive to phospholipids. Multiple transcript variants encoding different isoforms have been found for this gene. This gene was originally known as ARFGAP1, but that is now the name of a related but different gene. [provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.792
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARFGAP3 | NM_014570.5 | c.836A>G | p.Tyr279Cys | missense_variant | 10/16 | ENST00000263245.10 | |
ARFGAP3 | NM_001142293.2 | c.704A>G | p.Tyr235Cys | missense_variant | 9/15 | ||
ARFGAP3 | XM_005261525.5 | c.836A>G | p.Tyr279Cys | missense_variant | 10/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARFGAP3 | ENST00000263245.10 | c.836A>G | p.Tyr279Cys | missense_variant | 10/16 | 1 | NM_014570.5 | P1 | |
ARFGAP3 | ENST00000437119.6 | c.704A>G | p.Tyr235Cys | missense_variant | 9/15 | 1 | |||
ARFGAP3 | ENST00000453516.5 | c.377A>G | p.Tyr126Cys | missense_variant | 5/8 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000810 AC: 2AN: 247050Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 133818
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GnomAD4 exome AF: 0.00000480 AC: 7AN: 1458776Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4AN XY: 725800
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74350
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Gain of methylation at K280 (P = 0.0134);.;
MVP
MPC
ClinPred
D
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