Variant 1-219193161-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138794.5(LYPLAL1):c.271C>G(p.Leu91Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

LYPLAL1
NM_138794.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1008831).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYPLAL1	NM_138794.5 linkuse as main transcript	c.271C>G	p.Leu91Val	missense_variant	3/5	ENST00000366928.10	NP_620149.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYPLAL1	ENST00000366928.10 linkuse as main transcript	c.271C>G	p.Leu91Val	missense_variant	3/5	1	NM_138794.5	ENSP00000355895	P1	Q5VWZ2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

250202

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135254

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000327

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:

0.00000411

AC:

AN:

1458902

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725802

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

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

Mar 18, 2024

The c.271C>G (p.L91V) alteration is located in exon 3 (coding exon 3) of the LYPLAL1 gene. This alteration results from a C to G substitution at nucleotide position 271, causing the leucine (L) at amino acid position 91 to be replaced by a valine (V). 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

0.088

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0055

T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.0063

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.90

N;N

REVEL

Benign

0.041

Sift

Benign

0.37

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.0010

B;B

Vest4

0.32

MutPred

0.55

Loss of helix (P = 0.3949);.;

MVP

0.38

MPC

0.0030

ClinPred

0.067

GERP RS

3.6

Varity_R

0.39

gMVP

0.45

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