rs34400049

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018046.5(AGGF1):​c.2092C>A​(p.Pro698Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,613,404 control chromosomes in the GnomAD database, including 61,144 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.23 ( 4484 hom., cov: 31)
Exomes 𝑓: 0.27 ( 56660 hom. )

Consequence

AGGF1
NM_018046.5 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0200
Variant links:
Genes affected
AGGF1 (HGNC:24684): (angiogenic factor with G-patch and FHA domains 1) This gene encodes an angiogenic factor that promotes proliferation of endothelial cells. Mutations in this gene are associated with a susceptibility to Klippel-Trenaunay syndrome. Pseudogenes of this gene are found on chromosomes 3, 4, 10 and 16.[provided by RefSeq, Sep 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0029018223).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AGGF1NM_018046.5 linkuse as main transcriptc.2092C>A p.Pro698Thr missense_variant 14/14 ENST00000312916.12 NP_060516.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AGGF1ENST00000312916.12 linkuse as main transcriptc.2092C>A p.Pro698Thr missense_variant 14/141 NM_018046.5 ENSP00000316109 P1Q8N302-1

Frequencies

GnomAD3 genomes
AF:
0.227
AC:
34486
AN:
151756
Hom.:
4487
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0979
Gnomad AMI
AF:
0.277
Gnomad AMR
AF:
0.276
Gnomad ASJ
AF:
0.281
Gnomad EAS
AF:
0.273
Gnomad SAS
AF:
0.138
Gnomad FIN
AF:
0.264
Gnomad MID
AF:
0.269
Gnomad NFE
AF:
0.287
Gnomad OTH
AF:
0.266
GnomAD3 exomes
AF:
0.254
AC:
63729
AN:
251232
Hom.:
8725
AF XY:
0.251
AC XY:
34069
AN XY:
135816
show subpopulations
Gnomad AFR exome
AF:
0.0928
Gnomad AMR exome
AF:
0.283
Gnomad ASJ exome
AF:
0.277
Gnomad EAS exome
AF:
0.267
Gnomad SAS exome
AF:
0.135
Gnomad FIN exome
AF:
0.265
Gnomad NFE exome
AF:
0.292
Gnomad OTH exome
AF:
0.268
GnomAD4 exome
AF:
0.274
AC:
400174
AN:
1461528
Hom.:
56660
Cov.:
40
AF XY:
0.270
AC XY:
196247
AN XY:
727086
show subpopulations
Gnomad4 AFR exome
AF:
0.0954
Gnomad4 AMR exome
AF:
0.284
Gnomad4 ASJ exome
AF:
0.278
Gnomad4 EAS exome
AF:
0.272
Gnomad4 SAS exome
AF:
0.136
Gnomad4 FIN exome
AF:
0.270
Gnomad4 NFE exome
AF:
0.290
Gnomad4 OTH exome
AF:
0.267
GnomAD4 genome
AF:
0.227
AC:
34489
AN:
151876
Hom.:
4484
Cov.:
31
AF XY:
0.226
AC XY:
16767
AN XY:
74226
show subpopulations
Gnomad4 AFR
AF:
0.0978
Gnomad4 AMR
AF:
0.275
Gnomad4 ASJ
AF:
0.281
Gnomad4 EAS
AF:
0.273
Gnomad4 SAS
AF:
0.138
Gnomad4 FIN
AF:
0.264
Gnomad4 NFE
AF:
0.287
Gnomad4 OTH
AF:
0.269
Alfa
AF:
0.279
Hom.:
9694
Bravo
AF:
0.227
TwinsUK
AF:
0.287
AC:
1066
ALSPAC
AF:
0.296
AC:
1140
ESP6500AA
AF:
0.0999
AC:
440
ESP6500EA
AF:
0.291
AC:
2499
ExAC
AF:
0.248
AC:
30163
Asia WGS
AF:
0.215
AC:
749
AN:
3478
EpiCase
AF:
0.291
EpiControl
AF:
0.295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.76
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
6.6
DANN
Benign
0.18
DEOGEN2
Benign
0.0056
T
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.51
T
MetaRNN
Benign
0.0029
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.050
N
REVEL
Benign
0.045
Sift
Benign
0.89
T
Sift4G
Benign
0.96
T
Polyphen
0.22
B
Vest4
0.0090
MPC
0.21
ClinPred
0.0016
T
GERP RS
1.6
Varity_R
0.034
gMVP
0.20

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34400049; hg19: chr5-76359024; COSMIC: COSV57227721; API