17-19948562-G-T

Variant names:

• chr17-19948562-G-T
• rs169412
• NM_007202.4:c.878-1057C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007202.4(AKAP10):​c.878-1057C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,796 control chromosomes in the GnomAD database, including 14,361 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (14361 hom., cov: 30)
• Consequence: AKAP10 NM_007202.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857
• Publications: 3 publications found

Genes affected

AKAP10 (HGNC:368): (A-kinase anchoring protein 10) This gene encodes a member of the A-kinase anchor protein family. A-kinase anchor proteins bind to the regulatory subunits of protein kinase A (PKA) and confine the holoenzyme to discrete locations within the cell. The encoded protein is localized to mitochondria and interacts with both the type I and type II regulatory subunits of PKA. Polymorphisms in this gene may be associated with increased risk of arrhythmias and sudden cardiac death. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007202.4. 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
	AKAP10	NM_007202.4	MANE Select	c.878-1057C>A		intron	N/A	NP_009133.2
	AKAP10	NM_001330152.2		c.878-1057C>A		intron	N/A	NP_001317081.1	E7EMD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP10	ENST00000225737.11	TSL:1 MANE Select	c.878-1057C>A		intron	N/A	ENSP00000225737.6	O43572
	AKAP10	ENST00000395536.7	TSL:5	c.878-1057C>A		intron	N/A	ENSP00000378907.3	E7EMD6
	AKAP10	ENST00000941090.1		c.878-1057C>A		intron	N/A	ENSP00000611149.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64225 AN: 151678 Hom.: 14337 Cov.: 30

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.411

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.424 AC: 64302 AN: 151796 Hom.: 14361 Cov.: 30 AF XY: 0.420 AC XY: 31169 AN XY: 74128

African (AFR) AF: 0.569 AC: 23557 AN: 41400

American (AMR) AF: 0.429 AC: 6535 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3466

East Asian (EAS) AF: 0.189 AC: 976 AN: 5154

South Asian (SAS) AF: 0.287 AC: 1377 AN: 4800

European-Finnish (FIN) AF: 0.349 AC: 3662 AN: 10494

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.377 AC: 25596 AN: 67956

Other (OTH) AF: 0.410 AC: 865 AN: 2108

Alfa AF: 0.325 Hom.: 1244

Bravo AF: 0.439

Asia WGS AF: 0.238 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.64
PhyloP100		-0.86
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: rs169412; hg19: chr17-19851875;