dbSNP rs113234838: AGAP6:p.Lys264ArgfsTer10 (chr10-50008914-CAA-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.47

Variant links:

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]

AGAP6 links:

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]

TIMM23B-AGAP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP6	NM_001077665.3 link	c.791_792delAA	p.Lys264ArgfsTer10	frameshift_variant	Exon 8 of 8	ENST00000412531.7	NP_001071133.2	Q5VW22-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGAP6	ENST00000412531.7 link	c.791_792delAA	p.Lys264ArgfsTer10	frameshift_variant	Exon 8 of 8	1	NM_001077665.3	ENSP00000500374.1	Q5VW22-2
TIMM23B-AGAP6	ENST00000651763.1 link	n.1006_1007delAA		non_coding_transcript_exon_variant	Exon 17 of 18			ENSP00000502214.1
TIMM23B-AGAP6	ENST00000651763.1 link	n.1006_1007delAA		3_prime_UTR_variant	Exon 17 of 18			ENSP00000502214.1

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28710

AN:

151782

Hom.:

3254

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.202

AC:

49341

AN:

244796

Hom.:

5844

AF XY:

0.207

AC XY:

27688

AN XY:

133706

show subpopulations

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 SAS exome

AF:

0.173

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

show subpopulations

Gnomad4 AFR exome

AF:

0.0626

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.0535

Gnomad4 SAS exome

AF:

0.177

Gnomad4 FIN exome

AF:

0.227

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.232

GnomAD4 genome

AF:

0.189

AC:

28720

AN:

151898

Hom.:

3256

Cov.:

AF XY:

0.186

AC XY:

13837

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.0727

Gnomad4 AMR

AF:

0.166

Gnomad4 ASJ

AF:

0.259

Gnomad4 EAS

AF:

0.0435

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.268

Gnomad4 OTH

AF:

0.202

Alfa

AF:

0.235

Hom.:

771

Bravo

AF:

0.177

EpiCase

AF:

0.271

EpiControl

AF:

0.259

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over