1-243624707-A-C

Position:

• chr1-243624707-A-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKT3	NM_005465.7	c.562-9546T>G		intron_variant		ENST00000673466.1	NP_005456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT3	ENST00000673466.1	c.562-9546T>G		intron_variant			NM_005465.7	ENSP00000500582	P1
FABP7P1	ENST00000424004.1	n.350T>G		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR exome AF: 0.00629

Gnomad4 AMR exome AF: 0.00615

Gnomad4 ASJ exome AF: 0.0195

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.0831

Gnomad4 FIN exome AF: 0.0175

Gnomad4 NFE exome AF: 0.0315

Gnomad4 OTH exome AF: 0.0240

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

Gnomad4 AFR AF: 0.00544

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.0917

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.0303

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0256 Hom.: 12

Bravo AF: 0.0251

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.5
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs12032481; hg19: chr1-243788009; COSMIC: COSV55614084;