NM_001276343.3:c.1703G>A

Variant names:

• chr10-45826273-C-T
• rs1484096310
• NM_001276343.3:c.1703G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001276343.3(AGAP4):​c.1703G>A​(p.Arg568His) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0055 (2 hom., cov: 23)
  • Exomes 𝑓: 0.00066 (8 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGAP4 NM_001276343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86

Genes affected

AGAP4 (HGNC:23459): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 4) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in regulation of catalytic activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PARGP1-AGAP4 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007595688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP4	NM_001276343.3	c.1703G>A	p.Arg568His	missense_variant	Exon 8 of 8	ENST00000616763.6	NP_001263272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP4	ENST00000616763.6	c.1703G>A	p.Arg568His	missense_variant	Exon 8 of 8	1	NM_001276343.3	ENSP00000483751.2
AGAP4	ENST00000448048.7	c.1634G>A	p.Arg545His	missense_variant	Exon 7 of 7	1		ENSP00000392513.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 815 AN: 147416 Hom.: 2 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00129

Gnomad ASJ AF: 0.000298

Gnomad EAS AF: 0.000405

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000759

Gnomad OTH AF: 0.00400

GnomAD3 exomes AF: 0.00168 AC: 72 AN: 42942 Hom.: 21 AF XY: 0.000984 AC XY: 21 AN XY: 21352

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.000734

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.000655 AC: 954 AN: 1456486 Hom.: 8 Cov.: 30 AF XY: 0.000582 AC XY: 422 AN XY: 724542

Gnomad4 AFR exome AF: 0.0195

Gnomad4 AMR exome AF: 0.00128

Gnomad4 ASJ exome AF: 0.000539

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000233

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000116

Gnomad4 OTH exome AF: 0.00128

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00552 AC: 814 AN: 147530 Hom.: 2 Cov.: 23 AF XY: 0.00533 AC XY: 382 AN XY: 71686

Gnomad4 AFR AF: 0.0191

Gnomad4 AMR AF: 0.00128

Gnomad4 ASJ AF: 0.000298

Gnomad4 EAS AF: 0.000406

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000759

Gnomad4 OTH AF: 0.00396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.9
DANN	Benign	0.72
DEOGEN2	Benign	0.087	T;.;.;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.0076	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.6	M;.;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.7	D;.;.;.
REVEL	Benign	0.17
Sift	Benign	0.21	T;.;.;.
Sift4G	Benign	0.085	T;T;T;T
Polyphen		0.015	B;.;.;.
Vest4		0.17
MVP		0.040
ClinPred		0.080	T
Varity_R		0.16
gMVP		0.044

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: rs1484096310; hg19: chr10-46321721;