Variant 1-219211559-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138794.5(LYPLAL1):c.545T>C(p.Val182Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000102 in 1,613,286 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

LYPLAL1
NM_138794.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76

Variant links:

Genes affected

LYPLAL1 (HGNC:20440): (lysophospholipase like 1) Predicted to enable carboxylic ester hydrolase activity and palmitoyl-(protein) hydrolase activity. Predicted to be involved in protein depalmitoylation. Predicted to act upstream of or within negative regulation of Golgi to plasma membrane protein transport. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LYPLAL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYPLAL1	NM_138794.5 linkuse as main transcript	c.545T>C	p.Val182Ala	missense_variant	5/5	ENST00000366928.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYPLAL1	ENST00000366928.10 linkuse as main transcript	c.545T>C	p.Val182Ala	missense_variant	5/5	1	NM_138794.5	P1	Q5VWZ2-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

250866

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000106

AC:

155

AN:

1461180

Hom.:

Cov.:

AF XY:

0.0000935

AC XY:

AN XY:

726888

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000637

Gnomad4 NFE exome

AF:

0.0000963

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000961

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000296

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 submitter

clinical testing

Ambry Genetics

Dec 20, 2021

The c.545T>C (p.V182A) alteration is located in exon 5 (coding exon 5) of the LYPLAL1 gene. This alteration results from a T to C substitution at nucleotide position 545, causing the valine (V) at amino acid position 182 to be replaced by an alanine (A). 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

0.86

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.045

T;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.062

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.48

MutPred

0.80

Loss of stability (P = 0.0282);.;

MVP

0.57

MPC

0.0095

ClinPred

0.61

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.84

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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