Variant 8-54052660-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006330.4(LYPLA1):c.457C>T(p.Pro153Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 1,612,002 control chromosomes in the GnomAD database, including 347 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.027 ( 187 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 160 hom. )

Consequence

LYPLA1
NM_006330.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.65

Variant links:

Genes affected

LYPLA1 (HGNC:6737): (lysophospholipase 1) This gene encodes a member of the alpha/beta hydrolase superfamily. The encoded protein functions as a homodimer, exhibiting both depalmitoylating as well as lysophospholipase activity, and may be involved in Ras localization and signaling. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 4, 6, and 7. [provided by RefSeq, Jul 2013]

LYPLA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024594963).

BP6

Variant 8-54052660-G-A is Benign according to our data. Variant chr8-54052660-G-A is described in ClinVar as [Benign]. Clinvar id is 783525.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYPLA1	NM_006330.4 linkuse as main transcript	c.457C>T	p.Pro153Ser	missense_variant	7/9	ENST00000316963.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYPLA1	ENST00000316963.8 linkuse as main transcript	c.457C>T	p.Pro153Ser	missense_variant	7/9	1	NM_006330.4	P1	O75608-1

Frequencies

GnomAD3 genomes

AF:

0.0265

AC:

4037

AN:

152096

Hom.:

187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0933

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00812

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00699

AC:

1756

AN:

251238

Hom.:

AF XY:

0.00514

AC XY:

698

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.0965

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00279

AC:

4067

AN:

1459788

Hom.:

160

Cov.:

AF XY:

0.00240

AC XY:

1741

AN XY:

726364

show subpopulations

Gnomad4 AFR exome

AF:

0.0996

Gnomad4 AMR exome

AF:

0.00445

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000116

Gnomad4 OTH exome

AF:

0.00597

GnomAD4 genome

AF:

0.0266

AC:

4048

AN:

152214

Hom.:

187

Cov.:

AF XY:

0.0263

AC XY:

1954

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0933

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00536

Hom.:

Bravo

AF:

0.0301

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0924

AC:

407

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00864

AC:

1049

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

T;.;.;.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

T;T;T;T;D

MetaRNN

Benign

0.0025

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.;.;.;.

MutationTaster

Benign

0.00016

P;P;P;P

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-6.0

D;.;D;D;D

REVEL

Benign

0.091

Sift

Benign

0.10

T;.;T;T;D

Sift4G

Benign

0.18

T;T;T;.;.

Polyphen

0.0060

B;.;B;.;.

Vest4

0.11

MVP

0.33

MPC

0.40

ClinPred

0.047

GERP RS

4.0

Varity_R

0.59

gMVP

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