5-77039633-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018046.5(AGGF1):​c.784C>T​(p.Pro262Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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. P262L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

AGGF1
NM_018046.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40
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 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=0.14167008).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AGGF1NM_018046.5 linkc.784C>T p.Pro262Ser missense_variant Exon 5 of 14 ENST00000312916.12 NP_060516.2 Q8N302-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AGGF1ENST00000312916.12 linkc.784C>T p.Pro262Ser missense_variant Exon 5 of 14 1 NM_018046.5 ENSP00000316109.7 Q8N302-1
AGGF1ENST00000502408.1 linkn.*510C>T non_coding_transcript_exon_variant Exon 5 of 5 1 ENSP00000420874.1 H0Y8F8
ENSG00000285000ENST00000646704.1 linkn.649C>T non_coding_transcript_exon_variant Exon 5 of 16 ENSP00000495089.1 A0A2R8YFF1
AGGF1ENST00000502408.1 linkn.*510C>T 3_prime_UTR_variant Exon 5 of 5 1 ENSP00000420874.1 H0Y8F8

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151950
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1460954
Hom.:
0
Cov.:
30
AF XY:
0.0000110
AC XY:
8
AN XY:
726770
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151950
Hom.:
0
Cov.:
33
AF XY:
0.0000270
AC XY:
2
AN XY:
74188
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.784C>T (p.P262S) alteration is located in exon 5 (coding exon 5) of the AGGF1 gene. This alteration results from a C to T substitution at nucleotide position 784, causing the proline (P) at amino acid position 262 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
21
DANN
Benign
0.91
DEOGEN2
Benign
0.0042
T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.12
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.64
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
0.62
N
REVEL
Benign
0.26
Sift
Benign
0.29
T
Sift4G
Benign
0.58
T
Polyphen
0.0050
B
Vest4
0.23
MutPred
0.18
Gain of phosphorylation at P262 (P = 0.0407);
MVP
0.82
MPC
0.19
ClinPred
0.44
T
GERP RS
5.1
Varity_R
0.053
gMVP
0.097

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1187275653; hg19: chr5-76335458; API