chr5-77035739-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.512C>T​(p.Ser171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,460,120 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: not found (cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

AGGF1
NM_018046.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14
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=0.16457641).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AGGF1NM_018046.5 linkc.512C>T p.Ser171Leu missense_variant Exon 3 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.512C>T p.Ser171Leu missense_variant Exon 3 of 14 1 NM_018046.5 ENSP00000316109.7 Q8N302-1
ENSG00000285000ENST00000646704.1 linkn.377C>T non_coding_transcript_exon_variant Exon 3 of 16 ENSP00000495089.1 A0A2R8YFF1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251126
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135750
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1460120
Hom.:
0
Cov.:
30
AF XY:
0.0000206
AC XY:
15
AN XY:
726446
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:
0.0000189
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000624
Hom.:
0
Bravo
AF:
0.00000378
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 18, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.512C>T (p.S171L) alteration is located in exon 3 (coding exon 3) of the AGGF1 gene. This alteration results from a C to T substitution at nucleotide position 512, causing the serine (S) at amino acid position 171 to be replaced by a leucine (L). 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
0.066
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T;.
Eigen
Benign
0.011
Eigen_PC
Benign
0.079
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.73
T;T
M_CAP
Benign
0.047
D
MetaRNN
Benign
0.16
T;T
MetaSVM
Uncertain
0.047
D
MutationAssessor
Uncertain
2.4
M;M
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-2.2
N;D
REVEL
Benign
0.12
Sift
Uncertain
0.015
D;D
Sift4G
Uncertain
0.047
D;D
Polyphen
0.84
P;B
Vest4
0.23
MutPred
0.18
Loss of disorder (P = 0.0272);Loss of disorder (P = 0.0272);
MVP
0.84
MPC
0.16
ClinPred
0.60
D
GERP RS
5.1
Varity_R
0.063
gMVP
0.25

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: rs756206014; hg19: chr5-76331564; API