1-243500591-C-T

Variant names:

• chr1-243500591-C-T
• rs14403
• NM_005465.7:c.*4658G>A

Variant summary

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

The NM_005465.7(AKT3):​c.*4658G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 228,610 control chromosomes in the GnomAD database, including 4,191 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 (2599 hom., cov: 32)
  • Exomes 𝑓: 0.20 (1592 hom.)
• Consequence: AKT3 NM_005465.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 39 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]

AKT3 Gene-Disease associations (from GenCC):

• overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

  Inheritance: AD Classification: STRONG Submitted by: G2P
• megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2

  Inheritance: AD Classification: STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• microcephaly

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 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.*4658G>A		3_prime_UTR	Exon 14 of 14	NP_005456.1	Q9Y243-1
	AKT3	NM_001370074.1		c.*4658G>A		3_prime_UTR	Exon 14 of 14	NP_001357003.1	Q9Y243-1
	AKT3	NM_001206729.2		c.1355-805G>A		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.*4658G>A		3_prime_UTR	Exon 14 of 14	ENSP00000500582.1	Q9Y243-1
	AKT3	ENST00000336199.9	TSL:1	c.1355-805G>A		intron	N/A	ENSP00000336943.5	Q9Y243-2
	AKT3	ENST00000366540.5	TSL:1	c.1355-805G>A		intron	N/A	ENSP00000355498.1	Q9Y243-2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26141 AN: 151940 Hom.: 2599 Cov.: 32

Gnomad AFR AF: 0.0830

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.198 AC: 15127 AN: 76552 Hom.: 1592 Cov.: 0 AF XY: 0.197 AC XY: 6930 AN XY: 35216

African (AFR) AF: 0.0820 AC: 303 AN: 3694

American (AMR) AF: 0.177 AC: 417 AN: 2354

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 801 AN: 4824

East Asian (EAS) AF: 0.220 AC: 2375 AN: 10786

South Asian (SAS) AF: 0.199 AC: 135 AN: 680

European-Finnish (FIN) AF: 0.148 AC: 8 AN: 54

Middle Eastern (MID) AF: 0.134 AC: 64 AN: 476

European-Non Finnish (NFE) AF: 0.208 AC: 9816 AN: 47268

Other (OTH) AF: 0.188 AC: 1208 AN: 6416

GnomAD4 genome AF: 0.172 AC: 26141 AN: 152058 Hom.: 2599 Cov.: 32 AF XY: 0.173 AC XY: 12875 AN XY: 74296

African (AFR) AF: 0.0827 AC: 3431 AN: 41476

American (AMR) AF: 0.163 AC: 2486 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 625 AN: 3466

East Asian (EAS) AF: 0.277 AC: 1428 AN: 5160

South Asian (SAS) AF: 0.200 AC: 965 AN: 4816

European-Finnish (FIN) AF: 0.195 AC: 2066 AN: 10568

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14486 AN: 67974

Other (OTH) AF: 0.174 AC: 366 AN: 2108

Alfa AF: 0.166 Hom.: 1112

Bravo AF: 0.167

Asia WGS AF: 0.211 AC: 736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.65
PhyloP100		-1.0
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: rs14403; hg19: chr1-243663893;