Variant 7-151120123-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031946.7(AGAP3):c.1106A>G(p.Lys369Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,210 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: 6.8e-7 ( 0 hom. )

Consequence

AGAP3
NM_031946.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.25

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15988639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGAP3	NM_031946.7 linkuse as main transcript	c.1106A>G	p.Lys369Arg	missense_variant	8/18	ENST00000397238.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGAP3	ENST00000397238.7 linkuse as main transcript	c.1106A>G	p.Lys369Arg	missense_variant	8/18	1	NM_031946.7	P1	Q96P47-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152132

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:

0.000193

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

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246944

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134018

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459960

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 11, 2023

The c.1106A>G (p.K369R) alteration is located in exon 8 (coding exon 8) of the AGAP3 gene. This alteration results from a A to G substitution at nucleotide position 1106, causing the lysine (K) at amino acid position 369 to be replaced by an arginine (R). 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

0.15

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.017

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

D;D;D;D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.16

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.2

N;N;N;.;N;N

REVEL

Benign

0.21

Sift

Benign

1.0

T;T;T;.;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0070, 0.22

.;.;B;.;B;.

Vest4

0.55

MutPred

0.30

.;.;.;.;Gain of sheet (P = 0.0043);.;

MVP

0.60

MPC

0.42

ClinPred

0.33

GERP RS

3.5

Varity_R

0.037

gMVP

0.28

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