chr10-45826273-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001276343.3(AGAP4):​c.1703G>T​(p.Arg568Leu) 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 0.000041 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000042 (2 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18014026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP4	NM_001276343.3	c.1703G>T	p.Arg568Leu	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>T	p.Arg568Leu	missense_variant	Exon 8 of 8	1	NM_001276343.3	ENSP00000483751.2
AGAP4	ENST00000448048.7	c.1634G>T	p.Arg545Leu	missense_variant	Exon 7 of 7	1		ENSP00000392513.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 6 AN: 147486 Hom.: 0 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.0000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000202

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000607

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000140 AC: 6 AN: 42942 Hom.: 2 AF XY: 0.0000937 AC XY: 2 AN XY: 21352

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00101

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: 0.0000419 AC: 61 AN: 1456630 Hom.: 2 Cov.: 30 AF XY: 0.0000469 AC XY: 34 AN XY: 724606

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000406

Gnomad4 OTH exome AF: 0.0000832

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000407 AC: 6 AN: 147486 Hom.: 0 Cov.: 23 AF XY: 0.0000698 AC XY: 5 AN XY: 71602

Gnomad4 AFR AF: 0.0000245

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000202

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000607

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T;.;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Pathogenic	3.5	M;.;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.6	D;.;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D;.;.;.
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		0.69	P;.;.;.
Vest4		0.36
MVP		0.22
ClinPred		0.46	T
Varity_R		0.56
gMVP		0.073

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;