chr10-50008914-CAA-C

Variant names:

• chr10-50008914-CAA-C
• rs113234838
• NM_001077665.3:c.791_792delAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001077665.3(AGAP6):​c.791_792delAA​(p.Lys264ArgfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,898 control chromosomes in the GnomAD database, including 3,256 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3256 hom., cov: 25)
  • Exomes 𝑓: 0.25 (46442 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGAP6 NM_001077665.3 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.47
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 10-50008914-CAA-C is Benign according to our data. Variant chr10-50008914-CAA-C is described in ClinVar as Benign. ClinVar VariationId is 769369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

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.791_792delAA	p.Lys264ArgfsTer10	frameshift	Exon 8 of 8	NP_001071133.2	Q5VW22-2
	TIMM23B-AGAP6	NR_158654.1		n.1296_1297delAA		non_coding_transcript_exon	Exon 13 of 13
	TIMM23B-AGAP6	NR_158656.1		n.1355_1356delAA		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP6	ENST00000412531.7	TSL:1 MANE Select	c.791_792delAA	p.Lys264ArgfsTer10	frameshift	Exon 8 of 8	ENSP00000500374.1	Q5VW22-2
	AGAP6	ENST00000374056.10	TSL:1	c.722_723delAA	p.Lys241ArgfsTer10	frameshift	Exon 7 of 7	ENSP00000363168.6	Q5VW22-1
	AGAP6	ENST00000311652.11	TSL:1	c.*374_*375delAA		3_prime_UTR	Exon 8 of 8	ENSP00000309985.8	A0A087WSV4

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28710 AN: 151782 Hom.: 3254 Cov.: 25

Gnomad AFR AF: 0.0726

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0440

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.205

GnomAD2 exomes AF: 0.202 AC: 49341 AN: 244796 AF XY: 0.207

Gnomad AFR exome AF: 0.0657

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.261

Gnomad EAS exome AF: 0.0374

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.227

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.246 AC: 358878 AN: 1461244 Hom.: 46442 AF XY: 0.245 AC XY: 178155 AN XY: 726980

African (AFR) AF: 0.0626 AC: 2094 AN: 33470

American (AMR) AF: 0.138 AC: 6155 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 6975 AN: 26132

East Asian (EAS) AF: 0.0535 AC: 2125 AN: 39700

South Asian (SAS) AF: 0.177 AC: 15288 AN: 86240

European-Finnish (FIN) AF: 0.227 AC: 12125 AN: 53408

Middle Eastern (MID) AF: 0.200 AC: 1155 AN: 5764

European-Non Finnish (NFE) AF: 0.269 AC: 298946 AN: 1111450

Other (OTH) AF: 0.232 AC: 14015 AN: 60370

GnomAD4 genome AF: 0.189 AC: 28720 AN: 151898 Hom.: 3256 Cov.: 25 AF XY: 0.186 AC XY: 13837 AN XY: 74206

African (AFR) AF: 0.0727 AC: 3013 AN: 41456

American (AMR) AF: 0.166 AC: 2537 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 899 AN: 3466

East Asian (EAS) AF: 0.0435 AC: 224 AN: 5146

South Asian (SAS) AF: 0.157 AC: 752 AN: 4800

European-Finnish (FIN) AF: 0.227 AC: 2398 AN: 10542

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18207 AN: 67924

Other (OTH) AF: 0.202 AC: 426 AN: 2112

Alfa AF: 0.235 Hom.: 771

Bravo AF: 0.177

EpiCase AF: 0.271

EpiControl AF: 0.259

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5
Mutation Taster		=187/13	polymorphism (auto)

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: rs113234838; hg19: chr10-51768674; COSMIC: COSV65017251;