rs12032481

Variant names:

• chr1-243624707-A-C
• rs12032481
• NM_005465.7:c.562-9546T>G

Variant summary

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

The NM_005465.7(AKT3):​c.562-9546T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 201,814 control chromosomes in the GnomAD database, including 173 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 0.026 (113 hom., cov: 31)
  • Exomes 𝑓: 0.036 (60 hom.)
• Consequence: AKT3 NM_005465.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 1 publications found

Genes affected

AKT3 (HGNC:393): (AKT serine/threonine kinase 3) The protein encoded by this gene is a member of the AKT, also called PKB, serine/threonine protein kinase family. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1). Alternatively splice transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

FABP7P1 (HGNC:41951): (fatty acid binding protein 7 pseudogene 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005465.7. 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
	AKT3	NM_005465.7	MANE Select	c.562-9546T>G		intron	N/A	NP_005456.1	Q9Y243-1
	AKT3	NM_001370074.1		c.562-9546T>G		intron	N/A	NP_001357003.1	Q9Y243-1
	AKT3	NM_001206729.2		c.562-9546T>G		intron	N/A	NP_001193658.1	Q9Y243-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKT3	ENST00000673466.1	MANE Select	c.562-9546T>G		intron	N/A	ENSP00000500582.1	Q9Y243-1
	AKT3	ENST00000263826.12	TSL:1	c.562-9546T>G		intron	N/A	ENSP00000263826.5	Q9Y243-1
	AKT3	ENST00000336199.9	TSL:1	c.562-9546T>G		intron	N/A	ENSP00000336943.5	Q9Y243-2

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4016 AN: 152190 Hom.: 113 Cov.: 31

Gnomad AFR AF: 0.00543

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0355 AC: 1758 AN: 49506 Hom.: 60 Cov.: 0 AF XY: 0.0381 AC XY: 1120 AN XY: 29414

African (AFR) AF: 0.00629 AC: 8 AN: 1272

American (AMR) AF: 0.00615 AC: 45 AN: 7318

Ashkenazi Jewish (ASJ) AF: 0.0195 AC: 15 AN: 770

East Asian (EAS) AF: 0.119 AC: 355 AN: 2972

South Asian (SAS) AF: 0.0831 AC: 407 AN: 4896

European-Finnish (FIN) AF: 0.0175 AC: 74 AN: 4240

Middle Eastern (MID) AF: 0.0199 AC: 24 AN: 1206

European-Non Finnish (NFE) AF: 0.0315 AC: 785 AN: 24956

Other (OTH) AF: 0.0240 AC: 45 AN: 1876

GnomAD4 genome AF: 0.0264 AC: 4018 AN: 152308 Hom.: 113 Cov.: 31 AF XY: 0.0269 AC XY: 2003 AN XY: 74482

African (AFR) AF: 0.00544 AC: 226 AN: 41554

American (AMR) AF: 0.0140 AC: 214 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3468

East Asian (EAS) AF: 0.128 AC: 664 AN: 5180

South Asian (SAS) AF: 0.0917 AC: 442 AN: 4820

European-Finnish (FIN) AF: 0.0183 AC: 194 AN: 10620

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0303 AC: 2060 AN: 68040

Other (OTH) AF: 0.0251 AC: 53 AN: 2114

Alfa AF: 0.0208 Hom.: 17

Bravo AF: 0.0251

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.5
DANN	Benign	0.63
PhyloP100		-0.57
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: rs12032481; hg19: chr1-243788009; COSMIC: COSV55614084;