NM_004504.5:c.71C>G

Variant names:

• chr2-227472492-C-G
• rs769003880
• NM_004504.5:c.71C>G

Variant summary

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

The NM_004504.5(AGFG1):​c.71C>G​(p.Pro24Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P24L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGFG1 NM_004504.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44
• Publications: 0 publications found

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]

ENSG00000306559 (HGNC:):

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGFG1	NM_004504.5	MANE Select	c.71C>G	p.Pro24Arg	missense	Exon 1 of 13	NP_004495.2
	AGFG1	NM_001135187.2		c.71C>G	p.Pro24Arg	missense	Exon 1 of 14	NP_001128659.1	P52594-4
	AGFG1	NM_001135188.2		c.71C>G	p.Pro24Arg	missense	Exon 1 of 13	NP_001128660.1	P52594-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGFG1	ENST00000310078.13	TSL:1 MANE Select	c.71C>G	p.Pro24Arg	missense	Exon 1 of 13	ENSP00000312059.7	P52594-1
	AGFG1	ENST00000409171.5	TSL:1	c.71C>G	p.Pro24Arg	missense	Exon 1 of 13	ENSP00000387218.1	P52594-3
	AGFG1	ENST00000373671.7	TSL:1	c.71C>G	p.Pro24Arg	missense	Exon 1 of 12	ENSP00000362775.3	P52594-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000459 AC: 1 AN: 217750 AF XY: 0.00000833

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000103

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.00e-7 AC: 1 AN: 1428766 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 710684

African (AFR) AF: 0.00 AC: 0 AN: 30112

American (AMR) AF: 0.00 AC: 0 AN: 41938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25066

East Asian (EAS) AF: 0.00 AC: 0 AN: 35280

South Asian (SAS) AF: 0.00 AC: 0 AN: 84030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095888

Other (OTH) AF: 0.00 AC: 0 AN: 58900

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.57	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.54	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.4
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.28
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.051	T
Polyphen		0.23	B
Vest4		0.50
MutPred		0.56		Gain of MoRF binding (P = 6e-04)
MVP		0.40
MPC		2.3
ClinPred		0.97	D
GERP RS		3.0
PromoterAI		0.036	Neutral
Varity_R		0.68
gMVP		0.86
Mutation Taster		=20/80	disease causing

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

Other links and lift over

dbSNP: rs769003880; hg19: chr2-228337208;