2-227533741-T-C

Variant names:

• chr2-227533741-T-C
• rs143989711
• NM_004504.5:c.1007T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004504.5(AGFG1):​c.1007T>C​(p.Ile336Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000198 in 1,613,572 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 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: AGFG1 NM_004504.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.28
• Publications: 1 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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05755061).

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.1007T>C	p.Ile336Thr	missense	Exon 7 of 13	NP_004495.2
	AGFG1	NM_001135187.2		c.1079T>C	p.Ile360Thr	missense	Exon 8 of 14	NP_001128659.1	P52594-4
	AGFG1	NM_001135188.2		c.1007T>C	p.Ile336Thr	missense	Exon 7 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.1007T>C	p.Ile336Thr	missense	Exon 7 of 13	ENSP00000312059.7	P52594-1
	AGFG1	ENST00000409171.5	TSL:1	c.1007T>C	p.Ile336Thr	missense	Exon 7 of 13	ENSP00000387218.1	P52594-3
	AGFG1	ENST00000373671.7	TSL:1	c.887T>C	p.Ile296Thr	missense	Exon 6 of 12	ENSP00000362775.3	P52594-2

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000224 AC: 56 AN: 250180 AF XY: 0.000192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.000556

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.000493

GnomAD4 exome AF: 0.000204 AC: 298 AN: 1461256 Hom.: 0 Cov.: 31 AF XY: 0.000208 AC XY: 151 AN XY: 726906

African (AFR) AF: 0.0000299 AC: 1 AN: 33446

American (AMR) AF: 0.000246 AC: 11 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86224

European-Finnish (FIN) AF: 0.000712 AC: 38 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000207 AC: 230 AN: 1111634

Other (OTH) AF: 0.000199 AC: 12 AN: 60372

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74486

African (AFR) AF: 0.0000481 AC: 2 AN: 41570

American (AMR) AF: 0.000262 AC: 4 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000136 Hom.: 0

Bravo AF: 0.000155

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000214 AC: 26

EpiCase AF: 0.0000546

EpiControl AF: 0.000297

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.087
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.33	T
Polyphen		0.68	P
Vest4		0.68
MVP		0.30
MPC		0.26
ClinPred		0.090	T
GERP RS		5.1
Varity_R		0.083
gMVP		0.30
Mutation Taster		=81/19	polymorphism

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: rs143989711; hg19: chr2-228398457;