Genetic Variant AGFG1:p.Pro24Leu (chr2-227472492-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004504.5(AGFG1):c.71C>T(p.Pro24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,766 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

AGFG1
NM_004504.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44

Publications

0 publications found

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:

ENSG00000306559 (HGNC:):

ENSG00000306559 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004504.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGFG1	NM_004504.5	MANE Select	c.71C>T	p.Pro24Leu	missense	Exon 1 of 13	NP_004495.2
AGFG1	NM_001135187.2		c.71C>T	p.Pro24Leu	missense	Exon 1 of 14	NP_001128659.1	P52594-4
AGFG1	NM_001135188.2		c.71C>T	p.Pro24Leu	missense	Exon 1 of 13	NP_001128660.1	P52594-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGFG1	ENST00000310078.13	TSL:1 MANE Select	c.71C>T	p.Pro24Leu	missense	Exon 1 of 13	ENSP00000312059.7	P52594-1
AGFG1	ENST00000409171.5	TSL:1	c.71C>T	p.Pro24Leu	missense	Exon 1 of 13	ENSP00000387218.1	P52594-3
AGFG1	ENST00000373671.7	TSL:1	c.71C>T	p.Pro24Leu	missense	Exon 1 of 12	ENSP00000362775.3	P52594-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000138

AC:

AN:

217750

AF XY:

0.0000167

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1428766

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710684

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30112

American (AMR)

AF:

0.00

AC:

AN:

41938

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25066

East Asian (EAS)

AF:

0.0000283

AC:

AN:

35280

South Asian (SAS)

AF:

0.00

AC:

AN:

84030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095888

Other (OTH)

AF:

0.00

AC:

AN:

58900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000826

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.52

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.58

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.8

PhyloP100

3.4

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.28

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.041

Polyphen

0.25

Vest4

0.50

MutPred

0.58

Loss of disorder (P = 0.0289)

MVP

0.46

MPC

1.7

ClinPred

0.79

GERP RS

3.0

PromoterAI

0.018

Neutral

(source)

Varity_R

0.63

gMVP

0.84

Mutation Taster

=19/81

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over