19-15400850-C-A

Position:

• chr19-15400850-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000397410.10(AKAP8L):​c.928G>T​(p.Gly310Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AKAP8L ENST00000397410.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP8L	NM_014371.4	c.928G>T	p.Gly310Trp	missense_variant	7/14	ENST00000397410.10	NP_055186.3
AKAP8L	NM_001291478.2	c.745G>T	p.Gly249Trp	missense_variant	7/14		NP_001278407.1
AKAP8L	NR_111971.2	n.891G>T		non_coding_transcript_exon_variant	8/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP8L	ENST00000397410.10	c.928G>T	p.Gly310Trp	missense_variant	7/14	1	NM_014371.4	ENSP00000380557	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Oct 25, 2023

The c.928G>T (p.G310W) alteration is located in exon 7 (coding exon 7) of the AKAP8L gene. This alteration results from a G to T substitution at nucleotide position 928, causing the glycine (G) at amino acid position 310 to be replaced by a tryptophan (W). 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	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	0.83	D
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.9	D;.
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.049	D;T
Polyphen		1.0	D;.
Vest4		0.62
MutPred		0.23		Gain of solvent accessibility (P = 0.0202);.;
MVP		0.67
MPC		1.4
ClinPred		1.0	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.089

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: chr19-15511661;