rs138479600

Variant names:

• chr7-151119983-T-G
• rs138479600
• NM_031946.7:c.970-4T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-151119983-T-G
• chr7-151119983-T-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_031946.7(AGAP3):​c.970-4T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00547 in 1,613,510 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0056 (25 hom.)
• Consequence: AGAP3 NM_031946.7 splice_region, intron
• Scores: Splicing: ADA: 0.00007824
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.23
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 7-151119983-T-G is Benign according to our data. Variant chr7-151119983-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2658181.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

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.970-4T>G		splice_region intron	N/A	NP_114152.3
	AGAP3	NM_001350102.2		c.970-4T>G		splice_region intron	N/A	NP_001337031.1
	AGAP3	NM_001281300.2		c.286-4T>G		splice_region intron	N/A	NP_001268229.1	Q96P47-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP3	ENST00000397238.7	TSL:1 MANE Select	c.970-4T>G		splice_region intron	N/A	ENSP00000380413.2	Q96P47-4
	AGAP3	ENST00000335367.7	TSL:1	c.1510-4T>G		splice_region intron	N/A	ENSP00000335589.3	E7ESL9
	AGAP3	ENST00000473312.5	TSL:1	c.970-4T>G		splice_region intron	N/A	ENSP00000418921.1	Q96P47-6

Frequencies

GnomAD3 genomes AF: 0.00401 AC: 611 AN: 152202 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00681

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00439 AC: 1081 AN: 246490 AF XY: 0.00448

Gnomad AFR exome AF: 0.000991

Gnomad AMR exome AF: 0.00244

Gnomad ASJ exome AF: 0.000903

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00590

Gnomad NFE exome AF: 0.00671

Gnomad OTH exome AF: 0.00567

GnomAD4 exome AF: 0.00562 AC: 8218 AN: 1461190 Hom.: 25 Cov.: 32 AF XY: 0.00563 AC XY: 4094 AN XY: 726970

African (AFR) AF: 0.000956 AC: 32 AN: 33476

American (AMR) AF: 0.00282 AC: 126 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.000613 AC: 16 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00209 AC: 180 AN: 86238

European-Finnish (FIN) AF: 0.00643 AC: 341 AN: 53022

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5764

European-Non Finnish (NFE) AF: 0.00652 AC: 7244 AN: 1111848

Other (OTH) AF: 0.00441 AC: 266 AN: 60368

GnomAD4 genome AF: 0.00401 AC: 611 AN: 152320 Hom.: 3 Cov.: 33 AF XY: 0.00364 AC XY: 271 AN XY: 74484

African (AFR) AF: 0.000914 AC: 38 AN: 41570

American (AMR) AF: 0.00255 AC: 39 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00480 AC: 51 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00681 AC: 463 AN: 68024

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00548 Hom.: 0

Bravo AF: 0.00368

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.9
DANN	Benign	0.85
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000078
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.020		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: rs138479600; hg19: chr7-150817070;