Variant 7-151086913-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000397238.7(AGAP3):c.172C>T(p.Pro58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000221 in 1,580,464 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000070 ( 1 hom. )

Consequence

AGAP3
ENST00000397238.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.709

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:

AGAP3 (HGNC:):

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=0.13138306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGAP3	NM_031946.7 linkuse as main transcript	c.172C>T	p.Pro58Ser	missense_variant	1/18	ENST00000397238.7	NP_114152.3	Q96P47-4Q86XV5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGAP3	ENST00000397238.7 linkuse as main transcript	c.172C>T	p.Pro58Ser	missense_variant	1/18	1	NM_031946.7	ENSP00000380413.2		Q96P47-4

Frequencies

GnomAD3 genomes

AF:

0.000165

AC:

AN:

151258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000532

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.000483

GnomAD3 exomes

AF:

0.0000367

AC:

AN:

217802

Hom.:

AF XY:

0.0000248

AC XY:

AN XY:

121176

show subpopulations

Gnomad AFR exome

AF:

0.000594

Gnomad AMR exome

AF:

0.0000333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000700

AC:

AN:

1429206

Hom.:

Cov.:

AF XY:

0.00000562

AC XY:

AN XY:

711494

show subpopulations

Gnomad4 AFR exome

AF:

0.000258

Gnomad4 AMR exome

AF:

0.0000243

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:

0.00

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.000165

AC:

AN:

151258

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

73856

show subpopulations

Gnomad4 AFR

AF:

0.000532

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000483

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.0000581

AC:

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

Apr 26, 2023

The c.172C>T (p.P58S) alteration is located in exon 1 (coding exon 1) of the AGAP3 gene. This alteration results from a C to T substitution at nucleotide position 172, causing the proline (P) at amino acid position 58 to be replaced by a serine (S). 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

0.058

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

.;.;.;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Pathogenic

0.85

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.0

.;.;.;N

MutationTaster

Benign

0.96

D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.090

N;N;N;.

REVEL

Benign

0.23

Sift

Benign

0.031

D;D;T;.

Sift4G

Uncertain

0.015

D;D;D;T

Polyphen

0.91, 0.94

.;P;P;.

Vest4

0.13

MutPred

0.28

Loss of catalytic residue at P57 (P = 0.0144);Loss of catalytic residue at P57 (P = 0.0144);Loss of catalytic residue at P57 (P = 0.0144);.;

MVP

0.71

MPC

1.4

ClinPred

0.087

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.13

gMVP

0.60

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