Variant 19-15380373-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000397410.10(AKAP8L):c.1690G>A(p.Gly564Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,570,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

AKAP8L
ENST00000397410.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Variant links:

Genes affected

AKAP8L (HGNC:29857): (A-kinase anchoring protein 8 like) Enables histone deacetylase binding activity and lamin binding activity. Involved in several processes, including mitotic chromosome condensation; regulation of histone modification; and regulation of mRNA export from nucleus. Located in chromatin; cytoplasm; and nuclear lumen. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

AKAP8L links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034257382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AKAP8L	NM_014371.4 linkuse as main transcript	c.1690G>A	p.Gly564Ser	missense_variant	14/14	ENST00000397410.10	NP_055186.3
AKAP8L	NM_001291478.2 linkuse as main transcript	c.1507G>A	p.Gly503Ser	missense_variant	14/14		NP_001278407.1
AKAP8L	NR_111971.2 linkuse as main transcript	n.1790G>A		non_coding_transcript_exon_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP8L	ENST00000397410.10 linkuse as main transcript	c.1690G>A	p.Gly564Ser	missense_variant	14/14	1	NM_014371.4	ENSP00000380557	P2	Q9ULX6-1
	ENST00000597164.2 linkuse as main transcript	n.98-682C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.0000270

AC:

AN:

185288

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

101028

show subpopulations

Gnomad AFR exome

AF:

0.000477

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000141

AC:

AN:

1418662

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

702730

show subpopulations

Gnomad4 AFR exome

AF:

0.000582

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.00000836

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.1690G>A (p.G564S) alteration is located in exon 14 (coding exon 14) of the AKAP8L gene. This alteration results from a G to A substitution at nucleotide position 1690, causing the glycine (G) at amino acid position 564 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

0.95

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.30

N;.

REVEL

Benign

0.030

Sift

Benign

0.050

D;.

Sift4G

Benign

0.068

T;T

Polyphen

0.084

B;.

Vest4

0.13

MutPred

0.15

Gain of phosphorylation at G564 (P = 0.0052);.;

MVP

0.49

MPC

0.42

ClinPred

0.13

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

gMVP

0.093

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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