chr7-92031540-A-T

Variant names:

• chr7-92031540-A-T
• rs747689685
• NM_005751.5:c.4274A>T

Variant summary

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

The NM_005751.5(AKAP9):​c.4274A>T​(p.Glu1425Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,354 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AKAP9 NM_005751.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05

Genes affected

AKAP9 (HGNC:379): (A-kinase anchoring protein 9) 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. Alternate splicing of this gene results in at least two isoforms that localize to the centrosome and the Golgi apparatus, and interact with numerous signaling proteins from multiple signal transduction pathways. These signaling proteins include type II protein kinase A, serine/threonine kinase protein kinase N, protein phosphatase 1, protein phosphatase 2a, protein kinase C-epsilon and phosphodiesterase 4D3. [provided by RefSeq, Aug 2008]

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 rank	MANE	Protein	UniProt
AKAP9	NM_005751.5	c.4274A>T	p.Glu1425Val	missense_variant	Exon 16 of 50	ENST00000356239.8	NP_005742.4
AKAP9	NM_147185.3	c.4274A>T	p.Glu1425Val	missense_variant	Exon 16 of 50		NP_671714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8	c.4274A>T	p.Glu1425Val	missense_variant	Exon 16 of 50	1	NM_005751.5	ENSP00000348573.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251138 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135750

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

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: 6.85e-7 AC: 1 AN: 1460354 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726576

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

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 Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.35	.;.;T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.86	D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-1.2	T
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.7	D;.;.;N
REVEL	Benign	0.089
Sift	Uncertain	0.0010	D;.;.;D
Sift4G	Uncertain	0.0060	.;D;D;.
Vest4		0.50
MVP		0.44
MPC		0.31
ClinPred		0.95	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs747689685; hg19: chr7-91660854;