rs146969737

Variant names:

• chr17-57105641-C-T
• rs146969737
• NM_003488.4:c.177C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-57105641-C-T
• chr17-57105641-C-A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003488.4(AKAP1):​c.177C>T​(p.Pro59Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000499 in 1,614,108 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (1 hom.)
• Consequence: AKAP1 NM_003488.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.40
• Publications: 0 publications found

Genes affected

AKAP1 (HGNC:367): (A-kinase anchoring protein 1) 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. The encoded protein binds to type I and type II regulatory subunits of PKA and anchors them to the mitochondrion. This protein is speculated to be involved in the cAMP-dependent signal transduction pathway and in directing RNA to a specific cellular compartment. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 17-57105641-C-T is Benign according to our data. Variant chr17-57105641-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2647950.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.4 with no splicing effect.
• BS2: High AC in GnomAd4 at 296 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003488.4. 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
	AKAP1	NM_003488.4	MANE Select	c.177C>T	p.Pro59Pro	synonymous	Exon 2 of 11	NP_003479.1	A0A140VK05
	AKAP1	NM_001242902.2		c.177C>T	p.Pro59Pro	synonymous	Exon 3 of 12	NP_001229831.1	Q92667-1
	AKAP1	NM_001242903.2		c.177C>T	p.Pro59Pro	synonymous	Exon 3 of 12	NP_001229832.1	Q92667-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP1	ENST00000337714.8	TSL:1 MANE Select	c.177C>T	p.Pro59Pro	synonymous	Exon 2 of 11	ENSP00000337736.3	Q92667-1
	AKAP1	ENST00000314126.4	TSL:1	c.177C>T	p.Pro59Pro	synonymous	Exon 2 of 7	ENSP00000314075.3	Q92667-2
	AKAP1	ENST00000964437.1		c.177C>T	p.Pro59Pro	synonymous	Exon 2 of 12	ENSP00000634496.1

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 290 AN: 152120 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00570

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000876 AC: 220 AN: 251232 AF XY: 0.000810

Gnomad AFR exome AF: 0.00481

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00419

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000348 AC: 509 AN: 1461870 Hom.: 1 Cov.: 77 AF XY: 0.000330 AC XY: 240 AN XY: 727236

African (AFR) AF: 0.00475 AC: 159 AN: 33480

American (AMR) AF: 0.000559 AC: 25 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00229 AC: 91 AN: 39700

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86256

European-Finnish (FIN) AF: 0.000842 AC: 45 AN: 53414

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0000944 AC: 105 AN: 1111998

Other (OTH) AF: 0.000911 AC: 55 AN: 60396

GnomAD4 genome AF: 0.00194 AC: 296 AN: 152238 Hom.: 4 Cov.: 32 AF XY: 0.00211 AC XY: 157 AN XY: 74436

African (AFR) AF: 0.00583 AC: 242 AN: 41520

American (AMR) AF: 0.000980 AC: 15 AN: 15302

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

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68010

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000932 Hom.: 0

Bravo AF: 0.00233

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.2
DANN	Benign	0.40
PhyloP100		-1.4
PromoterAI		-0.0092	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs146969737; hg19: chr17-55183002;