chr5-77039634-C-T

Variant names:

• chr5-77039634-C-T
• rs757432619
• NM_018046.5:c.785C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018046.5(AGGF1):​c.785C>T​(p.Pro262Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,612,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P262S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: AGGF1 NM_018046.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72
• Publications: 0 publications found

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]

ENSG00000285000 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1377373).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018046.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGGF1	NM_018046.5	MANE Select	c.785C>T	p.Pro262Leu	missense	Exon 5 of 14	NP_060516.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGGF1	ENST00000312916.12	TSL:1 MANE Select	c.785C>T	p.Pro262Leu	missense	Exon 5 of 14	ENSP00000316109.7	Q8N302-1
	AGGF1	ENST00000502408.1	TSL:1	n.*511C>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000420874.1	H0Y8F8
	ENSG00000285000	ENST00000646704.1		n.650C>T		non_coding_transcript_exon	Exon 5 of 16	ENSP00000495089.1	A0A2R8YFF1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151878 Hom.: 0 Cov.: 33

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250808 AF XY: 0.0000147

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1460870 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 726738

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39554

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1111434

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151878 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74146

African (AFR) AF: 0.0000242 AC: 1 AN: 41312

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3470

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.7
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.24
Sift	Benign	0.12	T
Sift4G	Benign	0.24	T
Polyphen		0.028	B
Vest4		0.32
MutPred		0.24		Gain of sheet (P = 0.0266)
MVP		0.77
MPC		0.19
ClinPred		0.098	T
GERP RS		5.1
Varity_R		0.029
gMVP		0.11
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs757432619; hg19: chr5-76335459;