chr17-19936311-C-T

Variant names:

• chr17-19936311-C-T
• rs375240401
• NM_007202.4:c.1442G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_007202.4(AKAP10):​c.1442G>A​(p.Arg481His) variant causes a missense change. The variant allele was found at a frequency of 0.0000539 in 1,613,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: AKAP10 NM_007202.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3694545).
• BS2: High AC in GnomAdExome4 at 84 AD gene.

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.1442G>A	p.Arg481His	missense	Exon 9 of 15	NP_009133.2
	AKAP10	NM_001330152.2		c.1442G>A	p.Arg481His	missense	Exon 9 of 14	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.1442G>A	p.Arg481His	missense	Exon 9 of 15	ENSP00000225737.6	O43572
	AKAP10	ENST00000395536.7	TSL:5	c.1442G>A	p.Arg481His	missense	Exon 9 of 14	ENSP00000378907.3	E7EMD6
	AKAP10	ENST00000941090.1		c.1442G>A	p.Arg481His	missense	Exon 9 of 16	ENSP00000611149.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000677 AC: 17 AN: 250924 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000575 AC: 84 AN: 1461448 Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30 AN XY: 726998

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.000179 AC: 8 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000657 AC: 73 AN: 1111732

Other (OTH) AF: 0.0000166 AC: 1 AN: 60374

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74306

African (AFR) AF: 0.0000483 AC: 2 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000453

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.45
MVP		0.36
MPC		0.29
ClinPred		0.12	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.56
Mutation Taster		=62/38	polymorphism

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

Other links and lift over

dbSNP: rs375240401; hg19: chr17-19839624; COSMIC: COSV99855562; COSMIC: COSV99855562;