10-49988737-CGT-TTA

Variant names:

• chr10-49988737-CGT-TTA
• NM_001077665.3:c.22_24delCGTinsTTA
• AGAP6 p.Arg8Leu

Variant summary

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

The NM_001077665.3(AGAP6):​c.22_24delCGTinsTTA​(p.Arg8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: AGAP6 NM_001077665.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99
• 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.

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.22_24delCGTinsTTA	p.Arg8Leu	missense	N/A	NP_001071133.2	Q5VW22-2
	AGAP6	NR_171667.1		n.370_372delCGTinsTTA		non_coding_transcript_exon	Exon 1 of 9
	TIMM23B-AGAP6	NR_158654.1		n.729-571_729-569delCGTinsTTA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP6	ENST00000412531.7	TSL:1 MANE Select	c.22_24delCGTinsTTA	p.Arg8Leu	missense	N/A	ENSP00000500374.1	Q5VW22-2
	AGAP6	ENST00000374056.10	TSL:1	c.22_24delCGTinsTTA	p.Arg8Leu	missense	N/A	ENSP00000363168.6	Q5VW22-1
	AGAP6	ENST00000311652.11	TSL:1	c.22_24delCGTinsTTA	p.Arg8Leu	missense	N/A	ENSP00000309985.8	A0A087WSV4

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

Splicing

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: chr10-51748497;