rs1063243

Variant names:

• chr7-92097613-A-C
• rs1063243
• NM_005751.5:c.10426A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-92097613-A-C
• chr7-92097613-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005751.5(AKAP9):​c.10426A>C​(p.Arg3476Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,613,192 control chromosomes in the GnomAD database, including 125,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13845 hom., cov: 32)
  • Exomes 𝑓: 0.39 (111551 hom.)
• Consequence: AKAP9 NM_005751.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.907
• Publications: 34 publications found

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]

CYP51A1 (HGNC:2649): (cytochrome P450 family 51 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum protein participates in the synthesis of cholesterol by catalyzing the removal of the 14alpha-methyl group from lanosterol. Homologous genes are found in all three eukaryotic phyla, fungi, plants, and animals, suggesting that this is one of the oldest cytochrome P450 genes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

CYP51A1 Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 7-92097613-A-C is Benign according to our data. Variant chr7-92097613-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.907 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005751.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP9	NM_005751.5	MANE Select	c.10426A>C	p.Arg3476Arg	synonymous	Exon 42 of 50	NP_005742.4
	AKAP9	NM_147185.3		c.10402A>C	p.Arg3468Arg	synonymous	Exon 42 of 50	NP_671714.1	Q99996-3
	AKAP9	NM_001379277.1		c.5071A>C	p.Arg1691Arg	synonymous	Exon 21 of 29	NP_001366206.1	A0A2R8Y590

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP9	ENST00000356239.8	TSL:1 MANE Select	c.10426A>C	p.Arg3476Arg	synonymous	Exon 42 of 50	ENSP00000348573.3	Q99996-2
	AKAP9	ENST00000491695.2	TSL:1	c.5071A>C	p.Arg1691Arg	synonymous	Exon 21 of 29	ENSP00000494626.2	A0A2R8Y590
	AKAP9	ENST00000394534.7	TSL:1	c.3418A>C	p.Arg1140Arg	synonymous	Exon 15 of 23	ENSP00000378042.3	H7BYL6

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63548 AN: 151976 Hom.: 13826 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.425

GnomAD2 exomes AF: 0.380 AC: 95376 AN: 251212 AF XY: 0.381

Gnomad AFR exome AF: 0.531

Gnomad AMR exome AF: 0.312

Gnomad ASJ exome AF: 0.548

Gnomad EAS exome AF: 0.171

Gnomad FIN exome AF: 0.392

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.394

GnomAD4 exome AF: 0.387 AC: 565882 AN: 1461098 Hom.: 111551 Cov.: 47 AF XY: 0.387 AC XY: 281564 AN XY: 726868

African (AFR) AF: 0.531 AC: 17770 AN: 33462

American (AMR) AF: 0.317 AC: 14171 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 14181 AN: 26134

East Asian (EAS) AF: 0.185 AC: 7328 AN: 39686

South Asian (SAS) AF: 0.390 AC: 33598 AN: 86204

European-Finnish (FIN) AF: 0.387 AC: 20656 AN: 53414

Middle Eastern (MID) AF: 0.426 AC: 2284 AN: 5358

European-Non Finnish (NFE) AF: 0.389 AC: 432131 AN: 1111766

Other (OTH) AF: 0.394 AC: 23763 AN: 60350

GnomAD4 genome AF: 0.418 AC: 63619 AN: 152094 Hom.: 13845 Cov.: 32 AF XY: 0.415 AC XY: 30875 AN XY: 74344

African (AFR) AF: 0.525 AC: 21791 AN: 41468

American (AMR) AF: 0.363 AC: 5548 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1890 AN: 3472

East Asian (EAS) AF: 0.174 AC: 899 AN: 5180

South Asian (SAS) AF: 0.387 AC: 1865 AN: 4818

European-Finnish (FIN) AF: 0.385 AC: 4067 AN: 10564

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26335 AN: 67996

Other (OTH) AF: 0.425 AC: 898 AN: 2114

Alfa AF: 0.400 Hom.: 44605

Bravo AF: 0.422

Asia WGS AF: 0.316 AC: 1102 AN: 3478

EpiCase AF: 0.393

EpiControl AF: 0.403

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Long QT syndrome 11 (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Congenital long QT syndrome (1)
-	-	1	Long QT syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.9
DANN	Benign	0.53
PhyloP100		0.91
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1063243; hg19: chr7-91726927; COSMIC: COSV62342471; COSMIC: COSV62342471;