rs967614714

Variant names:

• chr7-151087022-A-G
• rs967614714
• NM_031946.7:c.281A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

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=0.26331282).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP3	NM_031946.7	MANE Select	c.281A>G	p.Glu94Gly	missense	Exon 1 of 18	NP_114152.3
	AGAP3	NM_001350102.2		c.281A>G	p.Glu94Gly	missense	Exon 1 of 16	NP_001337031.1
	AGAP3	NM_001042535.4		c.281A>G	p.Glu94Gly	missense	Exon 1 of 9	NP_001036000.1	Q96P47-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP3	ENST00000397238.7	TSL:1 MANE Select	c.281A>G	p.Glu94Gly	missense	Exon 1 of 18	ENSP00000380413.2	Q96P47-4
	AGAP3	ENST00000473312.5	TSL:1	c.281A>G	p.Glu94Gly	missense	Exon 1 of 9	ENSP00000418921.1	Q96P47-6
	AGAP3	ENST00000961568.1		c.281A>G	p.Glu94Gly	missense	Exon 1 of 19	ENSP00000631627.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111534

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000611 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.24
Sift	Benign	0.083	T
Sift4G	Benign	0.16	T
Polyphen		0.0020	B
Vest4		0.25
MVP		0.73
MPC		1.8
ClinPred		0.55	D
GERP RS		2.4
PromoterAI		-0.095	Neutral
Varity_R		0.093
gMVP		0.96
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs967614714; hg19: chr7-150784109;