rs767054513

Variant names:

• chr17-19936281-G-C
• rs767054513
• NM_007202.4:c.1467+5C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-19936281-G-C
• chr17-19936281-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007202.4(AKAP10):​c.1467+5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AKAP10 NM_007202.4 splice_region, intron
• Scores: Splicing: ADA: 0.00009950
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.1467+5C>G		splice_region intron	N/A	NP_009133.2
	AKAP10	NM_001330152.2		c.1467+5C>G		splice_region 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.1467+5C>G		splice_region intron	N/A	ENSP00000225737.6	O43572
	AKAP10	ENST00000395536.7	TSL:5	c.1467+5C>G		splice_region intron	N/A	ENSP00000378907.3	E7EMD6
	AKAP10	ENST00000937770.1		c.1472C>G	p.Thr491Ser	missense	Exon 9 of 16	ENSP00000607829.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454852 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723210

African (AFR) AF: 0.00 AC: 0 AN: 33168

American (AMR) AF: 0.00 AC: 0 AN: 43356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25836

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.00 AC: 0 AN: 85194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108616

Other (OTH) AF: 0.00 AC: 0 AN: 60082

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.054
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: rs767054513; hg19: chr17-19839594;