Variant chr19-15380387-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014371.4(AKAP8L):c.1676A>C(p.Gln559Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,431,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

AKAP8L
NM_014371.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.733

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09047055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AKAP8L	NM_014371.4 linkuse as main transcript	c.1676A>C	p.Gln559Pro	missense_variant	14/14	ENST00000397410.10
AKAP8L	NM_001291478.2 linkuse as main transcript	c.1493A>C	p.Gln498Pro	missense_variant	14/14
AKAP8L	NR_111971.2 linkuse as main transcript	n.1776A>C		non_coding_transcript_exon_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP8L	ENST00000397410.10 linkuse as main transcript	c.1676A>C	p.Gln559Pro	missense_variant	14/14	1	NM_014371.4	P2	Q9ULX6-1
	ENST00000597164.2 linkuse as main transcript	n.98-668T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000492

AC:

AN:

203192

Hom.:

AF XY:

0.00000903

AC XY:

AN XY:

110766

show subpopulations

Gnomad AFR exome

AF:

0.0000856

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:

0.0000119

AC:

AN:

1431188

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

709758

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

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:

0.0000146

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000224

Hom.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00000831

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

Aug 08, 2022

The c.1676A>C (p.Q559P) alteration is located in exon 14 (coding exon 14) of the AKAP8L gene. This alteration results from a A to C substitution at nucleotide position 1676, causing the glutamine (Q) at amino acid position 559 to be replaced by a proline (P). 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

0.056

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.051

T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

0.85

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.039

Sift

Benign

0.11

T;.

Sift4G

Benign

0.20

T;T

Polyphen

0.0

B;.

Vest4

0.18

MutPred

0.16

Gain of loop (P = 0);.;

MVP

0.32

MPC

0.52

ClinPred

0.17

GERP RS

2.4

Varity_R

0.36

gMVP

0.22

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