Variant chr18-62716274-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_194449.4(PHLPP1):c.591C>T(p.His197=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,530,834 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0018 ( 4 hom. )

Consequence

PHLPP1
NM_194449.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.439

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]

PHLPP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 18-62716274-C-T is Benign according to our data. Variant chr18-62716274-C-T is described in ClinVar as [Benign]. Clinvar id is 715064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.439 with no splicing effect.

BS2

High AC in GnomAd4 at 146 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHLPP1	NM_194449.4 linkuse as main transcript	c.591C>T	p.His197=	synonymous_variant	1/17	ENST00000262719.10	NP_919431.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHLPP1	ENST00000262719.10 linkuse as main transcript	c.591C>T	p.His197=	synonymous_variant	1/17	1	NM_194449.4	ENSP00000262719	P1	O60346-1

Frequencies

GnomAD3 genomes

AF:

0.000960

AC:

146

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000379

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00175

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000797

AC:

AN:

124156

Hom.:

AF XY:

0.000763

AC XY:

AN XY:

68154

show subpopulations

Gnomad AFR exome

AF:

0.000200

Gnomad AMR exome

AF:

0.000171

Gnomad ASJ exome

AF:

0.000126

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000465

Gnomad FIN exome

AF:

0.000683

Gnomad NFE exome

AF:

0.00173

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00182

AC:

2505

AN:

1378720

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1195

AN XY:

680312

show subpopulations

Gnomad4 AFR exome

AF:

0.000293

Gnomad4 AMR exome

AF:

0.000255

Gnomad4 ASJ exome

AF:

0.0000400

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000255

Gnomad4 FIN exome

AF:

0.00102

Gnomad4 NFE exome

AF:

0.00221

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.000960

AC:

146

AN:

152114

Hom.:

Cov.:

AF XY:

0.000901

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000379

Gnomad4 NFE

AF:

0.00175

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.8

DANN

Benign

0.97

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.

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