rs2353005

Positions:

• chr19-49869505-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098633.4(AKT1S1):​c.*412C>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 0.103 in 158,598 control chromosomes in the GnomAD database, including 1,018 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 0.10 (947 hom., cov: 33)
  • Exomes 𝑓: 0.12 (71 hom.)
• Consequence: AKT1S1 NM_001098633.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776

Genes affected

AKT1S1 (HGNC:28426): (AKT1 substrate 1) AKT1S1 is a proline-rich substrate of AKT (MIM 164730) that binds 14-3-3 protein (see YWHAH, MIM 113508) when phosphorylated (Kovacina et al., 2003 [PubMed 12524439]).[supplied by OMIM, Mar 2008]

PNKP (HGNC:9154): (polynucleotide kinase 3'-phosphatase) This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5' phosphorylation and 3' dephosphorylation of nucleic acids. Mutations at this locus have been associated with microcephaly, seizures, and developmental delay.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKT1S1	NM_001098633.4	c.*412C>T		3_prime_UTR_variant	5/5	ENST00000344175.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKT1S1	ENST00000344175.10	c.*412C>T		3_prime_UTR_variant	5/5	3	NM_001098633.4	P4

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15487 AN: 152190 Hom.: 949 Cov.: 33

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0926

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0912

Gnomad FIN AF: 0.0888

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.125 AC: 786 AN: 6290 Hom.: 71 Cov.: 0 AF XY: 0.123 AC XY: 405 AN XY: 3284

Gnomad4 AFR exome AF: 0.0504

Gnomad4 AMR exome AF: 0.0556

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.0896

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.102 AC: 15477 AN: 152308 Hom.: 947 Cov.: 33 AF XY: 0.0991 AC XY: 7382 AN XY: 74476

Gnomad4 AFR AF: 0.0364

Gnomad4 AMR AF: 0.0923

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0919

Gnomad4 FIN AF: 0.0888

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.111

Alfa AF: 0.136 Hom.: 1554

Bravo AF: 0.101

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.47
DANN	Benign	0.69

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: rs2353005; hg19: chr19-50372762;