Genetic Variant NM_001077665.3:c.127G>A (chr10-49988842-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001077665.3(AGAP6):c.127G>A(p.Ala43Thr) 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. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A43S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Consequence

AGAP6
NM_001077665.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.967

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:

ENSG00000285803 (HGNC:):

ENSG00000285803 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06608188).

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.127G>A	p.Ala43Thr	missense	Exon 1 of 8	NP_001071133.2	Q5VW22-2
TIMM23B-AGAP6	NR_158658.1		n.890G>A		non_coding_transcript_exon	Exon 8 of 15
TIMM23B-AGAP6	NR_158660.1		n.1073G>A		non_coding_transcript_exon	Exon 10 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGAP6	ENST00000412531.7	TSL:1 MANE Select	c.127G>A	p.Ala43Thr	missense	Exon 1 of 8	ENSP00000500374.1	Q5VW22-2
AGAP6	ENST00000374056.10	TSL:1	c.127G>A	p.Ala43Thr	missense	Exon 1 of 7	ENSP00000363168.6	Q5VW22-1
AGAP6	ENST00000311652.11	TSL:1	c.127G>A	p.Ala43Thr	missense	Exon 1 of 8	ENSP00000309985.8	A0A087WSV4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Benign

9.6

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0077

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.60

M_CAP

Benign

0.022

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.81

PhyloP100

0.97

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.85

REVEL

Benign

0.24

Sift

Uncertain

0.012

Sift4G

Benign

0.13

Vest4

0.14

MutPred

0.15

Gain of glycosylation at A43 (P = 0.0076)

MVP

0.048

ClinPred

0.14

GERP RS

0.094

PromoterAI

0.0058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.032

Mutation Taster

=100/0

polymorphism

(source)

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

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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