Genetic Variant AGAP6:p.Gln95* (chr10-49989367-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001077665.3(AGAP6):c.283C>T(p.Gln95*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

AGAP6
NM_001077665.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGAP6	NM_001077665.3	MANE Select	c.283C>T	p.Gln95*	stop_gained	Exon 2 of 8	NP_001071133.2	Q5VW22-2
TIMM23B-AGAP6	NR_158654.1		n.788C>T		non_coding_transcript_exon	Exon 7 of 13
TIMM23B-AGAP6	NR_158656.1		n.847C>T		non_coding_transcript_exon	Exon 8 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGAP6	ENST00000412531.7	TSL:1 MANE Select	c.283C>T	p.Gln95*	stop_gained	Exon 2 of 8	ENSP00000500374.1	Q5VW22-2
AGAP6	ENST00000311652.11	TSL:1	c.283C>T	p.Gln95*	stop_gained	Exon 2 of 8	ENSP00000309985.8	A0A087WSV4
AGAP6	ENST00000374056.10	TSL:1	c.223+429C>T		intron	N/A	ENSP00000363168.6	Q5VW22-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33400

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111718

Other (OTH)

AF:

0.00

AC:

AN:

60116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

(source)

DANN

Benign

0.56

Eigen

Uncertain

0.35

Eigen_PC

Benign

0.011

FATHMM_MKL

Benign

0.48

PhyloP100

2.0

Vest4

0.051

GERP RS

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=131/69

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over