rs6967

Variant names:

• chr17-57121059-C-T
• rs6967
• NM_003488.4:c.*735C>T

Variant summary

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

The NM_003488.4(AKAP1):​c.*735C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,486 control chromosomes in the GnomAD database, including 2,295 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 0.17 (2288 hom., cov: 32)
  • Exomes 𝑓: 0.16 (7 hom.)
• Consequence: AKAP1 NM_003488.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP1	NM_003488.4	MANE Select	c.*735C>T		3_prime_UTR	Exon 11 of 11	NP_003479.1
	AKAP1	NM_001242902.2		c.*735C>T		3_prime_UTR	Exon 12 of 12	NP_001229831.1
	AKAP1	NM_001242903.2		c.*735C>T		3_prime_UTR	Exon 12 of 12	NP_001229832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP1	ENST00000337714.8	TSL:1 MANE Select	c.*735C>T		3_prime_UTR	Exon 11 of 11	ENSP00000337736.3
	AKAP1	ENST00000964437.1		c.*735C>T		3_prime_UTR	Exon 12 of 12	ENSP00000634496.1
	AKAP1	ENST00000964438.1		c.*735C>T		3_prime_UTR	Exon 12 of 12	ENSP00000634497.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25356 AN: 152030 Hom.: 2281 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.0945

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.160 AC: 54 AN: 338 Hom.: 7 Cov.: 0 AF XY: 0.181 AC XY: 37 AN XY: 204

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.164 AC: 53 AN: 324

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.167 AC: 25402 AN: 152148 Hom.: 2288 Cov.: 32 AF XY: 0.165 AC XY: 12306 AN XY: 74380

African (AFR) AF: 0.241 AC: 9998 AN: 41486

American (AMR) AF: 0.127 AC: 1935 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3472

East Asian (EAS) AF: 0.0962 AC: 498 AN: 5178

South Asian (SAS) AF: 0.0958 AC: 462 AN: 4822

European-Finnish (FIN) AF: 0.168 AC: 1782 AN: 10590

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9791 AN: 67986

Other (OTH) AF: 0.157 AC: 332 AN: 2112

Alfa AF: 0.149 Hom.: 3059

Bravo AF: 0.166

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		1.9
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: rs6967; hg19: chr17-55198420;