AGAP6 p.Gly35Arg

Variant names:

• chr10-49988818-G-C
• NM_001077665.3:c.103G>C
• AGAP6 p.Gly35Arg

Your query was ambiguous. Multiple possible variants found:

• chr10-49988818-G-C
• chr10-49988818-G-A
• chr10-49988818-GGA-CGT
• chr10-49988818-GGA-CGC
• chr10-49988818-GGA-CGG
• chr10-49988818-GGA-AGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077665.3(AGAP6):​c.103G>C​(p.Gly35Arg) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: AGAP6 NM_001077665.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 0 publications found

Genes affected

AGAP6 (HGNC:23466): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 6) 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]

TIMM23B-AGAP6 (HGNC:45009): (TIMM23B-AGAP6 readthrough (NMD candidate)) This locus represents naturally-occurring readthrough transcription between the adjacent TIMM23B (translocase of inner mitochondrial membrane 23 homolog B) and AGAP6 (ArfGAP with GTPase domain, ankyrin repeat and PH domain 6) genes. Readthrough transcripts contain portions of the coding sequence for both genes and are predicted to be candidates for nonsense-mediated decay (NMD). [provided by RefSeq, Sep 2018]

ENSG00000285803 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15481284).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077665.3. 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
	AGAP6	NM_001077665.3	MANE Select	c.103G>C	p.Gly35Arg	missense	Exon 1 of 8	NP_001071133.2	Q5VW22-2
	TIMM23B-AGAP6	NR_158658.1		n.866G>C		non_coding_transcript_exon	Exon 8 of 15
	TIMM23B-AGAP6	NR_158660.1		n.1049G>C		non_coding_transcript_exon	Exon 10 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP6	ENST00000412531.7	TSL:1 MANE Select	c.103G>C	p.Gly35Arg	missense	Exon 1 of 8	ENSP00000500374.1	Q5VW22-2
	AGAP6	ENST00000374056.10	TSL:1	c.103G>C	p.Gly35Arg	missense	Exon 1 of 7	ENSP00000363168.6	Q5VW22-1
	AGAP6	ENST00000311652.11	TSL:1	c.103G>C	p.Gly35Arg	missense	Exon 1 of 8	ENSP00000309985.8	A0A087WSV4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00166 AC: 39 AN: 23460 AF XY: 0.00192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00204

Gnomad ASJ exome AF: 0.0231

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00215

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.25	T
PromoterAI		-0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.085
Mutation Taster		=98/2	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-51748578;