Variant 19-49872952-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001098633.4(AKT1S1):c.344C>A(p.Thr115Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AKT1S1
NM_001098633.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07

Variant links:

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]

AKT1S1 links:

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]

PNKP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18903476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKT1S1	NM_001098633.4 link	c.344C>A	p.Thr115Asn	missense_variant	2/5	ENST00000344175.10	NP_001092103.1	Q96B36-1A0A024QZF6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT1S1	ENST00000344175.10 link	c.344C>A	p.Thr115Asn	missense_variant	2/5	3	NM_001098633.4	ENSP00000341698.5		Q96B36-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451386

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721458

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.344C>A (p.T115N) alteration is located in exon 2 (coding exon 1) of the AKT1S1 gene. This alteration results from a C to A substitution at nucleotide position 344, causing the threonine (T) at amino acid position 115 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T;T;T;T;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.72

T;.;.;.;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.19

T;T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.69

N;N;N;N;N;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.070

N;N;N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.14

T;T;T;T;T;T

Sift4G

Benign

0.49

T;T;T;T;T;T

Polyphen

0.99

D;D;D;D;D;.

Vest4

0.28

MutPred

0.13

Loss of phosphorylation at T115 (P = 0.0546);Loss of phosphorylation at T115 (P = 0.0546);Loss of phosphorylation at T115 (P = 0.0546);Loss of phosphorylation at T115 (P = 0.0546);Loss of phosphorylation at T115 (P = 0.0546);.;

MVP

0.71

MPC

0.28

ClinPred

0.75

GERP RS

4.4

Varity_R

0.10

gMVP

0.099

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over