chr7-91940976-G-C

Position:

• chr7-91940976-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005751.5(AKAP9):​c.-124G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,022,494 control chromosomes in the GnomAD database, including 195,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26670 hom., cov: 34)
  • Exomes 𝑓: 0.62 (169104 hom.)
• Consequence: AKAP9 NM_005751.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.94

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-91940976-G-C is Benign according to our data. Variant chr7-91940976-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 360809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP9	NM_005751.5	c.-124G>C		5_prime_UTR_variant	1/50	ENST00000356239.8
AKAP9	NM_147185.3	c.-124G>C		5_prime_UTR_variant	1/50

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP9	ENST00000356239.8	c.-124G>C		5_prime_UTR_variant	1/50	1	NM_005751.5	P4

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89266 AN: 152062 Hom.: 26662 Cov.: 34

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.620 AC: 539689 AN: 870314 Hom.: 169104 Cov.: 11 AF XY: 0.619 AC XY: 280801 AN XY: 453286

Gnomad4 AFR exome AF: 0.496

Gnomad4 AMR exome AF: 0.687

Gnomad4 ASJ exome AF: 0.458

Gnomad4 EAS exome AF: 0.816

Gnomad4 SAS exome AF: 0.614

Gnomad4 FIN exome AF: 0.614

Gnomad4 NFE exome AF: 0.616

Gnomad4 OTH exome AF: 0.607

GnomAD4 genome AF: 0.587 AC: 89316 AN: 152180 Hom.: 26670 Cov.: 34 AF XY: 0.590 AC XY: 43885 AN XY: 74404

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.579

Alfa AF: 0.505 Hom.: 1558

Bravo AF: 0.585

Asia WGS AF: 0.686 AC: 2383 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Long QT syndrome 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Congenital long QT syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4727267; hg19: chr7-91570290;