19-15380549-G-A

Position:

• chr19-15380549-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000397410.10(AKAP8L):​c.1600C>T​(p.Leu534Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
• Consequence: AKAP8L ENST00000397410.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26518697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP8L	NM_014371.4	c.1600C>T	p.Leu534Phe	missense_variant	13/14	ENST00000397410.10	NP_055186.3
AKAP8L	NM_001291478.2	c.1417C>T	p.Leu473Phe	missense_variant	13/14		NP_001278407.1
AKAP8L	NR_111971.2	n.1700C>T		non_coding_transcript_exon_variant	15/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP8L	ENST00000397410.10	c.1600C>T	p.Leu534Phe	missense_variant	13/14	1	NM_014371.4	ENSP00000380557	P2
	ENST00000597164.2	n.98-506G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.1600C>T (p.L534F) alteration is located in exon 13 (coding exon 13) of the AKAP8L gene. This alteration results from a C to T substitution at nucleotide position 1600, causing the leucine (L) at amino acid position 534 to be replaced by a phenylalanine (F). 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	0.32
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T;.
Eigen	Benign	0.071
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	0.98	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.0	N;.
REVEL	Benign	0.056
Sift	Benign	0.21	T;.
Sift4G	Benign	0.069	T;T
Polyphen		0.66	P;.
Vest4		0.34
MutPred		0.48		Loss of catalytic residue at L534 (P = 0.0264);.;
MVP		0.29
MPC		1.3
ClinPred		0.95	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-15491360;