18-62716162-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_194449.4(PHLPP1):ā€‹c.479C>Gā€‹(p.Ser160Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,366,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.000011 ( 0 hom. )

Consequence

PHLPP1
NM_194449.4 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63
Variant links:
Genes affected
PHLPP1 (HGNC:20610): (PH domain and leucine rich repeat protein phosphatase 1) This gene encodes a member of the serine/threonine phosphatase family. The encoded protein promotes apoptosis by dephosphorylating and inactivating the serine/threonine kinase Akt, and functions as a tumor suppressor in multiple types of cancer. Increased expression of this gene may also play a role in obesity and type 2 diabetes by interfering with Akt-mediated insulin signaling. [provided by RefSeq, Dec 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.14888671).
BS2
High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PHLPP1NM_194449.4 linkuse as main transcriptc.479C>G p.Ser160Cys missense_variant 1/17 ENST00000262719.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PHLPP1ENST00000262719.10 linkuse as main transcriptc.479C>G p.Ser160Cys missense_variant 1/171 NM_194449.4 P1O60346-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000875
AC:
1
AN:
114350
Hom.:
0
AF XY:
0.0000158
AC XY:
1
AN XY:
63094
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000118
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:
0.0000110
AC:
15
AN:
1366730
Hom.:
0
Cov.:
32
AF XY:
0.0000178
AC XY:
12
AN XY:
673650
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000444
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.:
31
Bravo
AF:
0.0000264

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 submitterclinical testingAmbry GeneticsJun 22, 2023The c.479C>G (p.S160C) alteration is located in exon 1 (coding exon 1) of the PHLPP1 gene. This alteration results from a C to G substitution at nucleotide position 479, causing the serine (S) at amino acid position 160 to be replaced by a cysteine (C). 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
0.11
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.090
T
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.10
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.44
T
M_CAP
Pathogenic
0.39
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-0.46
N
REVEL
Benign
0.037
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.0090
D
Vest4
0.15
MutPred
0.19
Loss of glycosylation at S160 (P = 0.0018);
MVP
0.25
MPC
1.5
ClinPred
0.25
T
GERP RS
2.6
Varity_R
0.12
gMVP
0.15

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

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

Other links and lift over

dbSNP: rs1398021956; hg19: chr18-60383395; API