5-77046622-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_018046.5(AGGF1):c.1146T>C(p.Tyr382=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,614,038 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (27 hom.)
• Consequence: AGGF1 NM_018046.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.377

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-77046622-T-C is Benign according to our data. Variant chr5-77046622-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 777169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.377 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGGF1	NM_018046.5	c.1146T>C	p.Tyr382=	synonymous_variant	6/14	ENST00000312916.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGGF1	ENST00000312916.12	c.1146T>C	p.Tyr382=	synonymous_variant	6/14	1	NM_018046.5	P1

Frequencies

GnomAD3 genomes AF: 0.00367 AC: 559 AN: 152194 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0154

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00522

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00432 AC: 1086 AN: 251276 Hom.: 12 AF XY: 0.00421 AC XY: 572 AN XY: 135824

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.0177

Gnomad NFE exome AF: 0.00539

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00418 AC: 6110 AN: 1461726 Hom.: 27 Cov.: 32 AF XY: 0.00413 AC XY: 3000 AN XY: 727152

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00127

Gnomad4 ASJ exome AF: 0.000651

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000510

Gnomad4 FIN exome AF: 0.0177

Gnomad4 NFE exome AF: 0.00432

Gnomad4 OTH exome AF: 0.00388

GnomAD4 genome AF: 0.00367 AC: 559 AN: 152312 Hom.: 1 Cov.: 33 AF XY: 0.00379 AC XY: 282 AN XY: 74476

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0154

Gnomad4 NFE AF: 0.00522

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00452 Hom.: 2

Bravo AF: 0.00243

EpiCase AF: 0.00453

EpiControl AF: 0.00362

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2022	AGGF1: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Mar 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.032
Dann	Benign	0.33

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

Other links and lift over

dbSNP: rs61736982; hg19: chr5-76342447; COSMIC: COSV104397851;