chr5-77039594-C-T

Variant names:

• chr5-77039594-C-T
• rs747813682
• NM_018046.5:c.745C>T

Variant summary

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

The NM_018046.5(AGGF1):​c.745C>T​(p.Arg249Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,612,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: AGGF1 NM_018046.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94
• Publications: 1 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.

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.745C>T	p.Arg249Cys	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.745C>T	p.Arg249Cys	missense	Exon 5 of 14	ENSP00000316109.7	Q8N302-1
	AGGF1	ENST00000502408.1	TSL:1	n.*471C>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000420874.1	H0Y8F8
	ENSG00000285000	ENST00000646704.1		n.610C>T		non_coding_transcript_exon	Exon 5 of 16	ENSP00000495089.1	A0A2R8YFF1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152046 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: 0.0000399 AC: 10 AN: 250826 AF XY: 0.0000516

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1460664 Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18 AN XY: 726628

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.000302 AC: 26 AN: 86070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111394

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152046 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74246

African (AFR) AF: 0.0000242 AC: 1 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000741 AC: 9

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	0.21
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.54	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.9
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.79
MVP		0.89
MPC		0.84
ClinPred		0.73	D
GERP RS		4.0
Varity_R		0.21
gMVP		0.48
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs747813682; hg19: chr5-76335419;