Genetic Variant AKAP6:c.*3871G>T (chr14-32833676-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004274.5(AKAP6):c.*3871G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,934 control chromosomes in the GnomAD database, including 13,664 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 13664 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

AKAP6
NM_004274.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.263

Publications

37 publications found

Variant links:

Genes affected

AKAP6 (HGNC:376): (A-kinase anchoring protein 6) The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is highly expressed in various brain regions and cardiac and skeletal muscle. It is specifically localized to the sarcoplasmic reticulum and nuclear membrane, and is involved in anchoring PKA to the nuclear membrane or sarcoplasmic reticulum. [provided by RefSeq, Jul 2008]

AKAP6 links:

ENSG00000302430 (HGNC:):

ENSG00000302430 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004274.5. 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
	AKAP6	NM_004274.5	MANE Select	c.*3871G>T		3_prime_UTR	Exon 14 of 14	NP_004265.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKAP6	ENST00000280979.9	TSL:1 MANE Select	c.*3871G>T	3_prime_UTR	Exon 14 of 14	ENSP00000280979.4	Q13023-1
ENSG00000302430	ENST00000786608.1		n.278+8610C>A	intron	N/A
ENSG00000302430	ENST00000786609.1		n.214+5164C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63108

AN:

151816

Hom.:

13650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.435

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.416

AC:

63140

AN:

151934

Hom.:

13664

Cov.:

AF XY:

0.413

AC XY:

30643

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.299

AC:

12384

AN:

41434

American (AMR)

AF:

0.403

AC:

6161

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

1645

AN:

3470

East Asian (EAS)

AF:

0.371

AC:

1915

AN:

5164

South Asian (SAS)

AF:

0.447

AC:

2151

AN:

4814

European-Finnish (FIN)

AF:

0.458

AC:

4810

AN:

10506

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.480

AC:

32619

AN:

67944

Other (OTH)

AF:

0.442

AC:

934

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1856

3712

5567

7423

9279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.446

Hom.:

24074

Bravo

AF:

0.403

Asia WGS

AF:

0.477

AC:

1656

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.8

(source)

DANN

Benign

0.34

PhyloP100

0.26

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over