Variant 19-49871844-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001098633.4(AKT1S1):c.425C>G(p.Pro142Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,611,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

AKT1S1
NM_001098633.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.42

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKT1S1	NM_001098633.4 link	c.425C>G	p.Pro142Arg	missense_variant	Exon 3 of 5	ENST00000344175.10	NP_001092103.1	Q96B36-1A0A024QZF6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKT1S1	ENST00000344175.10 link	c.425C>G	p.Pro142Arg	missense_variant	Exon 3 of 5	3	NM_001098633.4	ENSP00000341698.5		Q96B36-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000483

AC:

AN:

248658

Hom.:

AF XY:

0.0000594

AC XY:

AN XY:

134688

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000610

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1459454

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000576

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.425C>G (p.P142R) alteration is located in exon 3 (coding exon 2) of the AKT1S1 gene. This alteration results from a C to G substitution at nucleotide position 425, causing the proline (P) at amino acid position 142 to be replaced by an arginine (R). 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

Pathogenic

0.72

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;D;D;D;D;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.79

T;.;.;.;.;T

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.49

T;T;T;T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.3

M;M;M;M;M;.

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-4.7

D;D;D;D;D;D

REVEL

Benign

0.29

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;.

Vest4

0.69

MVP

0.83

MPC

0.83

ClinPred

0.59

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over