Genetic Variant NM_031946.7:c.1120A>G (chr7-151120137-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031946.7(AGAP3):c.1120A>G(p.Ile374Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,608,834 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: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

AGAP3
NM_031946.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

Publications

0 publications found

Variant links:

Genes affected

AGAP3 (HGNC:16923): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 3) This gene encodes an essential component of the N-methyl-D-aspartate (NMDA) receptor signaling complex which mediates long-term potentiation in synapses by linking activation of NMDA receptor to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking. The encoded protein contains an N-terminal GTPase-like domain, a pleckstrin homology domain, an ArfGAP domain and several C-terminal ankryn repeat domains. [provided by RefSeq, Apr 2017]

AGAP3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1761755).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031946.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGAP3	NM_031946.7	MANE Select	c.1120A>G	p.Ile374Val	missense	Exon 8 of 18	NP_114152.3
AGAP3	NM_001350102.2		c.1120A>G	p.Ile374Val	missense	Exon 8 of 16	NP_001337031.1
AGAP3	NM_001281300.2		c.436A>G	p.Ile146Val	missense	Exon 8 of 16	NP_001268229.1	Q96P47-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGAP3	ENST00000397238.7	TSL:1 MANE Select	c.1120A>G	p.Ile374Val	missense	Exon 8 of 18	ENSP00000380413.2	Q96P47-4
AGAP3	ENST00000335367.7	TSL:1	c.1660A>G	p.Ile554Val	missense	Exon 8 of 9	ENSP00000335589.3	E7ESL9
AGAP3	ENST00000473312.5	TSL:1	c.1120A>G	p.Ile374Val	missense	Exon 8 of 9	ENSP00000418921.1	Q96P47-6

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151856

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

GnomAD2 exomes

AF:

0.00000820

AC:

AN:

243856

AF XY:

0.0000151

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1456978

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

724540

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

44306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25760

East Asian (EAS)

AF:

0.00

AC:

AN:

39548

South Asian (SAS)

AF:

0.00

AC:

AN:

85554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1109312

Other (OTH)

AF:

0.00

AC:

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

AF:

0.00000659

AC:

AN:

151856

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41342

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67906

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

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

Uncertain

0.56

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

Eigen

Benign

-0.080

Eigen_PC

Benign

-0.031

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.013

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

1.3

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.78

REVEL

Benign

0.021

Sift

Uncertain

0.020

Sift4G

Uncertain

0.0080

Polyphen

0.62

Vest4

0.44

MutPred

0.29

Loss of sheet (P = 0.0228)

MVP

0.40

MPC

0.59

ClinPred

0.29

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.064

gMVP

0.33

Mutation Taster

=50/50

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over