Variant 2-227533738-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004504.5(AGFG1):c.1004A>G(p.Asn335Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000576 in 1,613,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

AGFG1
NM_004504.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.55

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12892419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AGFG1	NM_004504.5 linkuse as main transcript	c.1004A>G	p.Asn335Ser	missense_variant	7/13	ENST00000310078.13
AGFG1	NM_001135187.2 linkuse as main transcript	c.1076A>G	p.Asn359Ser	missense_variant	8/14
AGFG1	NM_001135188.2 linkuse as main transcript	c.1004A>G	p.Asn335Ser	missense_variant	7/13
AGFG1	NM_001135189.2 linkuse as main transcript	c.884A>G	p.Asn295Ser	missense_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGFG1	ENST00000310078.13 linkuse as main transcript	c.1004A>G	p.Asn335Ser	missense_variant	7/13	1	NM_004504.5	P4	P52594-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000639

AC:

AN:

250266

Hom.:

AF XY:

0.0000739

AC XY:

AN XY:

135254

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000595

AC:

AN:

1461302

Hom.:

Cov.:

AF XY:

0.0000757

AC XY:

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000441

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000819

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.1076A>G (p.N359S) alteration is located in exon 8 (coding exon 8) of the AGFG1 gene. This alteration results from a A to G substitution at nucleotide position 1076, causing the asparagine (N) at amino acid position 359 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.15

Eigen_PC

Benign

0.050

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

D;D;T;D;D

M_CAP

Benign

0.045

MetaRNN

Benign

0.13

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.9

N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.30

T;T;T;T;T

Sift4G

Benign

0.71

T;T;T;T;T

Polyphen

0.0090, 0.64, 0.015

.;B;.;P;B

Vest4

0.51

MVP

0.25

MPC

0.12

ClinPred

0.080

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.24

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