Variant 2-227523801-T-C 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_004504.5(AGFG1):c.416T>C(p.Val139Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00826 in 1,613,940 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 80 hom. )

Consequence

AGFG1
NM_004504.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.38

Variant links:

Genes affected

AGFG1 (HGNC:5175): (ArfGAP with FG repeats 1) The protein encoded by this gene is related to nucleoporins, a class of proteins that mediate nucleocytoplasmic transport. The encoded protein binds the activation domain of the human immunodeficiency virus Rev protein when Rev is assembled onto its RNA target, and is required for the nuclear export of Rev-directed RNAs. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

AGFG1 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=0.009011686).

BP6

Variant 2-227523801-T-C is Benign according to our data. Variant chr2-227523801-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2651960.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AGFG1	NM_004504.5 linkuse as main transcript	c.416T>C	p.Val139Ala	missense_variant	4/13	ENST00000310078.13
AGFG1	NM_001135187.2 linkuse as main transcript	c.416T>C	p.Val139Ala	missense_variant	4/14
AGFG1	NM_001135188.2 linkuse as main transcript	c.416T>C	p.Val139Ala	missense_variant	4/13
AGFG1	NM_001135189.2 linkuse as main transcript	c.416T>C	p.Val139Ala	missense_variant	4/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGFG1	ENST00000310078.13 linkuse as main transcript	c.416T>C	p.Val139Ala	missense_variant	4/13	1	NM_004504.5	P4	P52594-1

Frequencies

GnomAD3 genomes

AF:

0.00482

AC:

733

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.000722

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00912

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00497

AC:

1248

AN:

251212

Hom.:

AF XY:

0.00508

AC XY:

690

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00282

Gnomad NFE exome

AF:

0.00981

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00862

AC:

12600

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00822

AC XY:

5977

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00358

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.00490

GnomAD4 genome

AF:

0.00482

AC:

733

AN:

152170

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

286

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.000721

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00912

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00822

Hom.:

Bravo

AF:

0.00462

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0117

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00907

AC:

ExAC

AF:

0.00542

AC:

658

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00742

EpiControl

AF:

0.00753

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

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

AGFG1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

D;D;D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.0090

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M;.;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.6

N;N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.21

T;T;T;T;T;T

Sift4G

Benign

0.60

T;T;T;T;T;T

Polyphen

0.063, 1.0, 0.10

.;B;.;D;B;.

Vest4

0.58

MVP

0.38

MPC

0.64

ClinPred

0.016

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.41

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