Genetic Variant AKAP10:p.Ile646Phe (chr17-19909228-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007202.4(AKAP10):c.1936A>T(p.Ile646Phe) 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. 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. I646V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AKAP10
NM_007202.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.39

Publications

0 publications found

Variant links:

Genes affected

AKAP10 (HGNC:368): (A-kinase anchoring protein 10) This gene encodes a member of the A-kinase anchor protein family. A-kinase anchor proteins bind to the regulatory subunits of protein kinase A (PKA) and confine the holoenzyme to discrete locations within the cell. The encoded protein is localized to mitochondria and interacts with both the type I and type II regulatory subunits of PKA. Polymorphisms in this gene may be associated with increased risk of arrhythmias and sudden cardiac death. [provided by RefSeq, May 2012]

AKAP10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2091133).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007202.4. 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
	AKAP10	NM_007202.4	MANE Select	c.1936A>T	p.Ile646Phe	missense	Exon 14 of 15	NP_009133.2
	AKAP10	NM_001330152.2		c.1762A>T	p.Ile588Phe	missense	Exon 13 of 14	NP_001317081.1	E7EMD6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AKAP10	ENST00000225737.11	TSL:1 MANE Select	c.1936A>T	p.Ile646Phe	missense	Exon 14 of 15	ENSP00000225737.6	O43572
AKAP10	ENST00000395536.7	TSL:5	c.1762A>T	p.Ile588Phe	missense	Exon 13 of 14	ENSP00000378907.3	E7EMD6
AKAP10	ENST00000941090.1		c.2062A>T	p.Ile688Phe	missense	Exon 15 of 16	ENSP00000611149.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1461278

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726948

African (AFR)

AF:

0.00

AC:

AN:

33438

American (AMR)

AF:

0.00

AC:

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111838

Other (OTH)

AF:

0.00

AC:

AN:

60366

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.57

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.0056

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.77

M_CAP

Benign

0.071

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

PhyloP100

3.4

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.17

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0070

Polyphen

0.026

Vest4

0.40

MutPred

0.33

Loss of MoRF binding (P = 0.1055)

MVP

0.22

MPC

0.36

ClinPred

0.91

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.45

gMVP

0.74

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