rs1484096310

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-45826273-C-G
• chr10-45826273-C-A
• chr10-45826273-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001276343.3(AGAP4):​c.1703G>C​(p.Arg568Pro) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R568C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGAP4 NM_001276343.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276343.3. 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
	AGAP4	NM_001276343.3	MANE Select	c.1703G>C	p.Arg568Pro	missense	Exon 8 of 8	NP_001263272.2	A0A087X0Z1
	AGAP4	NM_133446.4		c.1634G>C	p.Arg545Pro	missense	Exon 7 of 7	NP_597703.2	Q96P64
	AGAP4	NM_001393377.1		c.1586G>C	p.Arg529Pro	missense	Exon 10 of 10	NP_001380306.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP4	ENST00000616763.6	TSL:1 MANE Select	c.1703G>C	p.Arg568Pro	missense	Exon 8 of 8	ENSP00000483751.2	A0A087X0Z1
	AGAP4	ENST00000448048.7	TSL:1	c.1634G>C	p.Arg545Pro	missense	Exon 7 of 7	ENSP00000392513.2	Q96P64
	AGAP4	ENST00000970389.1		c.1697G>C	p.Arg566Pro	missense	Exon 8 of 8	ENSP00000640448.1

Frequencies

GnomAD3 genomes AF: 0.0000542 AC: 8 AN: 147486 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000473

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000500

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000275 AC: 4 AN: 1456640 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 724610

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4332

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109350

Other (OTH) AF: 0.0000666 AC: 4 AN: 60082

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000542 AC: 8 AN: 147486 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 71602

African (AFR) AF: 0.00 AC: 0 AN: 40790

American (AMR) AF: 0.000473 AC: 7 AN: 14786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3354

East Asian (EAS) AF: 0.00 AC: 0 AN: 4942

South Asian (SAS) AF: 0.00 AC: 0 AN: 4484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65892

Other (OTH) AF: 0.000500 AC: 1 AN: 2002

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

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	Pathogenic	0.80
BayesDel_addAF	Benign	-0.0090	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.0049
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0056	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	4.7	H
PhyloP100		3.9
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.94	P
Vest4		0.52
MVP		0.28
ClinPred		1.0	D
Varity_R		0.95
gMVP		0.28
Mutation Taster		=88/12	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: rs1484096310; hg19: chr10-46321721; COSMIC: COSV101432632; COSMIC: COSV101432632;