Variant 10-120589457-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001030059.3(PLPP4):c.771C>T(p.Ser257Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,613,724 control chromosomes in the GnomAD database, including 42,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3095 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39877 hom. )

Consequence

PLPP4
NM_001030059.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0260

Variant links:

Genes affected

PLPP4 (HGNC:23531): (phospholipid phosphatase 4) Enables diacylglycerol diphosphate phosphatase activity; identical protein binding activity; and phosphatidate phosphatase activity. Involved in phospholipid dephosphorylation and regulation of calcium ion import. Predicted to be located in plasma membrane. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

PLPP4 links:

PLPP4 (HGNC:):

PLPP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 10-120589457-C-T is Benign according to our data. Variant chr10-120589457-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2549582.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.026 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLPP4	NM_001030059.3 linkuse as main transcript	c.771C>T	p.Ser257Ser	synonymous_variant	7/7	ENST00000398250.6	NP_001025230.1	Q5VZY2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLPP4	ENST00000398250.6 linkuse as main transcript	c.771C>T	p.Ser257Ser	synonymous_variant	7/7	1	NM_001030059.3	ENSP00000381302.1		Q5VZY2-1
PLPP4	ENST00000369073.3 linkuse as main transcript	n.741C>T		non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29887

AN:

151994

Hom.:

3091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.0640

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.202

AC:

50375

AN:

249264

Hom.:

5439

AF XY:

0.207

AC XY:

27927

AN XY:

135224

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.186

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.0607

Gnomad SAS exome

AF:

0.256

Gnomad FIN exome

AF:

0.208

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.229

AC:

335416

AN:

1461612

Hom.:

39877

Cov.:

AF XY:

0.230

AC XY:

167043

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.183

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.0549

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.208

Gnomad4 NFE exome

AF:

0.243

Gnomad4 OTH exome

AF:

0.218

GnomAD4 genome

AF:

0.197

AC:

29921

AN:

152112

Hom.:

3095

Cov.:

AF XY:

0.197

AC XY:

14637

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.0644

Gnomad4 SAS

AF:

0.241

Gnomad4 FIN

AF:

0.215

Gnomad4 NFE

AF:

0.239

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.208

Hom.:

4288

Bravo

AF:

0.189

Asia WGS

AF:

0.201

AC:

699

AN:

3478

EpiCase

AF:

0.227

EpiControl

AF:

0.219

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 22, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

8.1

DANN

Benign

0.72

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