dbSNP rs750348682: AGAP3:p.Pro58Thr (chr7-151086913-C-A) – 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.172C>A(p.Pro58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. P58L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Consequence

AGAP3
NM_031946.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.709

Publications

1 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=0.26306036).

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.172C>A	p.Pro58Thr	missense	Exon 1 of 18	NP_114152.3
AGAP3	NM_001350102.2		c.172C>A	p.Pro58Thr	missense	Exon 1 of 16	NP_001337031.1
AGAP3	NM_001042535.4		c.172C>A	p.Pro58Thr	missense	Exon 1 of 9	NP_001036000.1	Q96P47-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGAP3	ENST00000397238.7	TSL:1 MANE Select	c.172C>A	p.Pro58Thr	missense	Exon 1 of 18	ENSP00000380413.2	Q96P47-4
AGAP3	ENST00000473312.5	TSL:1	c.172C>A	p.Pro58Thr	missense	Exon 1 of 9	ENSP00000418921.1	Q96P47-6
AGAP3	ENST00000961568.1		c.172C>A	p.Pro58Thr	missense	Exon 1 of 19	ENSP00000631627.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73856

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41328

American (AMR)

AF:

0.00

AC:

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67766

Other (OTH)

AF:

0.00

AC:

AN:

2072

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

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.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.76

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.26

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

-0.34

PhyloP100

0.71

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.12

REVEL

Benign

0.25

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0090

Polyphen

0.91

Vest4

0.23

MutPred

0.28

Loss of catalytic residue at P57 (P = 0.0144)

MVP

0.75

MPC

1.5

ClinPred

0.77

GERP RS

1.7

PromoterAI

0.00060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.18

gMVP

0.62

Mutation Taster

=65/35

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over