7-151087022-A-G

Position:

• chr7-151087022-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031946.7(AGAP3):​c.281A>G​(p.Glu94Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,460,658 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: not found (cov: 33)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: AGAP3 NM_031946.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.29

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]

ACMG classification

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=0.26331282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGAP3	NM_031946.7	c.281A>G	p.Glu94Gly	missense_variant	1/18	ENST00000397238.7	NP_114152.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGAP3	ENST00000397238.7	c.281A>G	p.Glu94Gly	missense_variant	1/18	1	NM_031946.7	ENSP00000380413.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1460658 Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13 AN XY: 726648

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: 0.0000252

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000611 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.281A>G (p.E94G) alteration is located in exon 1 (coding exon 1) of the AGAP3 gene. This alteration results from a A to G substitution at nucleotide position 281, causing the glutamic acid (E) at amino acid position 94 to be replaced by a glycine (G). 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	0.20
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	.;.;.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T;T;T;D
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	0.34	.;.;.;N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.8	N;N;N;.
REVEL	Benign	0.24
Sift	Benign	0.083	T;T;T;.
Sift4G	Benign	0.16	T;T;T;T
Polyphen		0.0020, 0.21	.;B;B;.
Vest4		0.25
MVP		0.73
MPC		1.8
ClinPred		0.55	D
GERP RS		2.4
Varity_R		0.093
gMVP		0.96

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

Other links and lift over

dbSNP: rs967614714; hg19: chr7-150784109;