rs138322898

Variant names:

• chr7-151086941-C-A
• rs138322898
• NM_031946.7:c.200C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-151086941-C-A
• chr7-151086941-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031946.7(AGAP3):​c.200C>A​(p.Ala67Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. A67V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AGAP3 NM_031946.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.45
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38300744).

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.200C>A	p.Ala67Glu	missense	Exon 1 of 18	NP_114152.3
	AGAP3	NM_001350102.2		c.200C>A	p.Ala67Glu	missense	Exon 1 of 16	NP_001337031.1
	AGAP3	NM_001042535.4		c.200C>A	p.Ala67Glu	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.200C>A	p.Ala67Glu	missense	Exon 1 of 18	ENSP00000380413.2	Q96P47-4
	AGAP3	ENST00000473312.5	TSL:1	c.200C>A	p.Ala67Glu	missense	Exon 1 of 9	ENSP00000418921.1	Q96P47-6
	AGAP3	ENST00000961568.1		c.200C>A	p.Ala67Glu	missense	Exon 1 of 19	ENSP00000631627.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.0020	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.4
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.25
Sift	Benign	0.048	D
Sift4G	Benign	0.16	T
Polyphen		0.66	P
Vest4		0.55
MutPred		0.35		Gain of sheet (P = 0.0149)
MVP		0.81
MPC		2.7
ClinPred		0.80	D
GERP RS		0.19
PromoterAI		0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.85
Mutation Taster		=73/27	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: rs138322898; hg19: chr7-150784028;