Variant 5-77035562-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_018046.5(AGGF1):c.335A>G(p.Tyr112Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000392 in 1,612,806 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

AGGF1
NM_018046.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.29

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]

AGGF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007969767).

BP6

Variant 5-77035562-A-G is Benign according to our data. Variant chr5-77035562-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 785128.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGGF1	NM_018046.5 linkuse as main transcript	c.335A>G	p.Tyr112Cys	missense_variant	3/14	ENST00000312916.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGGF1	ENST00000312916.12 linkuse as main transcript	c.335A>G	p.Tyr112Cys	missense_variant	3/14	1	NM_018046.5	P1	Q8N302-1
AGGF1	ENST00000506806.1 linkuse as main transcript	c.335A>G	p.Tyr112Cys	missense_variant	3/3	1			Q8N302-3
AGGF1	ENST00000502408.1 linkuse as main transcript	c.*61A>G		3_prime_UTR_variant, NMD_transcript_variant	3/5	1
AGGF1	ENST00000503538.5 linkuse as main transcript	n.352A>G		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

221

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000522

AC:

131

AN:

250744

Hom.:

AF XY:

0.000354

AC XY:

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.00508

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.000281

AC:

411

AN:

1460488

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

169

AN XY:

726636

show subpopulations

Gnomad4 AFR exome

AF:

0.00517

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00215

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000999

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.00146

AC:

222

AN:

152318

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00459

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000636

Hom.:

Bravo

AF:

0.00181

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000626

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000297

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.11

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.038

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.0080

T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.1

D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.013

B;B

Vest4

0.43

MVP

0.86

MPC

0.23

ClinPred

0.029

GERP RS

4.8

Varity_R

0.12

gMVP

0.23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over