rs1484096310

Variant summary

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

The NM_001276343.3(AGAP4):​c.1703G>C​(p.Arg568Pro) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R568C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., cov: 23)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

AGAP4
NM_001276343.3 missense

Scores

4
5
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.86

Publications

1 publications found
Variant links:
Genes affected
AGAP4 (HGNC:23459): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 4) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in regulation of catalytic activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276343.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
AGAP4
NM_001276343.3
MANE Select
c.1703G>Cp.Arg568Pro
missense
Exon 8 of 8NP_001263272.2A0A087X0Z1
AGAP4
NM_133446.4
c.1634G>Cp.Arg545Pro
missense
Exon 7 of 7NP_597703.2Q96P64
AGAP4
NM_001393377.1
c.1586G>Cp.Arg529Pro
missense
Exon 10 of 10NP_001380306.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
AGAP4
ENST00000616763.6
TSL:1 MANE Select
c.1703G>Cp.Arg568Pro
missense
Exon 8 of 8ENSP00000483751.2A0A087X0Z1
AGAP4
ENST00000448048.7
TSL:1
c.1634G>Cp.Arg545Pro
missense
Exon 7 of 7ENSP00000392513.2Q96P64
AGAP4
ENST00000970389.1
c.1697G>Cp.Arg566Pro
missense
Exon 8 of 8ENSP00000640448.1

Frequencies

GnomAD3 genomes
AF:
0.0000542
AC:
8
AN:
147486
Hom.:
0
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000473
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000500
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000275
AC:
4
AN:
1456640
Hom.:
0
Cov.:
30
AF XY:
0.00000414
AC XY:
3
AN XY:
724610
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33404
American (AMR)
AF:
0.00
AC:
0
AN:
44698
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25974
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86002
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53102
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4332
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1109350
Other (OTH)
AF:
0.0000666
AC:
4
AN:
60082
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000542
AC:
8
AN:
147486
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
71602
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
40790
American (AMR)
AF:
0.000473
AC:
7
AN:
14786
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3354
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4942
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4484
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10034
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
302
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
65892
Other (OTH)
AF:
0.000500
AC:
1
AN:
2002
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.406
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Benign
-0.0090
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
15
DANN
Benign
0.93
DEOGEN2
Benign
0.15
T
Eigen
Benign
0.0049
Eigen_PC
Benign
-0.36
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.0056
T
MetaRNN
Uncertain
0.54
D
MetaSVM
Benign
-0.41
T
MutationAssessor
Pathogenic
4.7
H
PhyloP100
3.9
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-5.7
D
REVEL
Benign
0.26
Sift
Uncertain
0.0020
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.94
P
Vest4
0.52
MVP
0.28
ClinPred
1.0
D
Varity_R
0.95
gMVP
0.28
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

dbSNP: rs1484096310; hg19: chr10-46321721; COSMIC: COSV101432632; COSMIC: COSV101432632; API