Variant 7-100562274-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006076.5(AGFG2):c.893C>T(p.Thr298Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,613,928 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 3 hom. )

Consequence

AGFG2
NM_006076.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

Variant links:

Genes affected

AGFG2 (HGNC:5177): (ArfGAP with FG repeats 2) This gene is a member of the HIV-1 Rev binding protein (HRB) family and encodes a protein with one Arf-GAP zinc finger domain, several phe-gly (FG) motifs, and four asn-pro-phe (NPF) motifs. This protein interacts with Eps15 homology (EH) domains and plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Feb 2013]

AGFG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.043143034).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AGFG2	NM_006076.5 linkuse as main transcript	c.893C>T	p.Thr298Ile	missense_variant	7/12	ENST00000300176.9	NP_006067.3
AGFG2	XM_005250306.3 linkuse as main transcript	c.926C>T	p.Thr309Ile	missense_variant	8/13		XP_005250363.1
AGFG2	XM_047420307.1 linkuse as main transcript	c.665C>T	p.Thr222Ile	missense_variant	8/13		XP_047276263.1
AGFG2	XM_047420308.1 linkuse as main transcript	c.191C>T	p.Thr64Ile	missense_variant	4/9		XP_047276264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGFG2	ENST00000300176.9 linkuse as main transcript	c.893C>T	p.Thr298Ile	missense_variant	7/12	1	NM_006076.5	ENSP00000300176	P1	O95081-1
AGFG2	ENST00000429987.1 linkuse as main transcript	c.119C>T	p.Thr40Ile	missense_variant	3/8	3		ENSP00000388594
AGFG2	ENST00000474713.1 linkuse as main transcript	n.548C>T		non_coding_transcript_exon_variant	5/9	5
AGFG2	ENST00000430857.5 linkuse as main transcript	c.*105C>T		3_prime_UTR_variant, NMD_transcript_variant	5/7	5		ENSP00000394453

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000317

AC:

AN:

249454

Hom.:

AF XY:

0.000392

AC XY:

AN XY:

135218

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000276

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000320

AC:

468

AN:

1461680

Hom.:

Cov.:

AF XY:

0.000375

AC XY:

273

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00157

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000271

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000151

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000330

Hom.:

Bravo

AF:

0.000215

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000371

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000652

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

Nov 08, 2022

The c.893C>T (p.T298I) alteration is located in exon 7 (coding exon 7) of the AGFG2 gene. This alteration results from a C to T substitution at nucleotide position 893, causing the threonine (T) at amino acid position 298 to be replaced by an isoleucine (I). 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

0.093

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0072

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.74

M_CAP

Benign

0.0099

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.7

REVEL

Benign

0.048

Sift

Uncertain

0.011

Sift4G

Benign

0.37

Polyphen

0.98

Vest4

0.30

MVP

0.47

MPC

0.42

ClinPred

0.057

GERP RS

4.8

Varity_R

0.11

gMVP

0.62

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