Variant 2-227536954-T-C 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.1339T>C(p.Ser447Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

AGFG1
NM_004504.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.92

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=0.16987374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AGFG1	NM_004504.5 linkuse as main transcript	c.1339T>C	p.Ser447Pro	missense_variant	10/13	ENST00000310078.13
AGFG1	NM_001135187.2 linkuse as main transcript	c.1411T>C	p.Ser471Pro	missense_variant	11/14
AGFG1	NM_001135188.2 linkuse as main transcript	c.1339T>C	p.Ser447Pro	missense_variant	10/13
AGFG1	NM_001135189.2 linkuse as main transcript	c.1219T>C	p.Ser407Pro	missense_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGFG1	ENST00000310078.13 linkuse as main transcript	c.1339T>C	p.Ser447Pro	missense_variant	10/13	1	NM_004504.5	P4	P52594-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251272

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460846

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Aug 22, 2023

The c.1411T>C (p.S471P) alteration is located in exon 11 (coding exon 11) of the AGFG1 gene. This alteration results from a T to C substitution at nucleotide position 1411, causing the serine (S) at amino acid position 471 to be replaced by a proline (P). 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

0.097

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Benign

-0.094

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.86

D;D;D;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.17

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-2.1

N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.13

T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.0070, 0.0010, 0.0040

.;B;.;B;B

Vest4

0.41

MutPred

0.24

.;Gain of relative solvent accessibility (P = 0.0023);.;.;Gain of relative solvent accessibility (P = 0.0023);

MVP

0.74

MPC

0.16

ClinPred

0.44

GERP RS

5.8

Varity_R

0.34

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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