rs149075251

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_138794.5(LYPLAL1):​c.82C>G​(p.His28Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H28Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

LYPLAL1
NM_138794.5 missense

Scores

8
8
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.11
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-DT (HGNC:50560): (LYPLAL1 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LYPLAL1NM_138794.5 linkc.82C>G p.His28Asp missense_variant Exon 1 of 5 ENST00000366928.10 NP_620149.2 Q5VWZ2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LYPLAL1ENST00000366928.10 linkc.82C>G p.His28Asp missense_variant Exon 1 of 5 1 NM_138794.5 ENSP00000355895.5 Q5VWZ2-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250208
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135346
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461756
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Uncertain
0.098
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
31
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T;.
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.81
T;T
M_CAP
Uncertain
0.18
D
MetaRNN
Pathogenic
0.98
D;D
MetaSVM
Uncertain
0.37
D
MutationAssessor
Pathogenic
3.5
M;M
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-7.4
D;D
REVEL
Pathogenic
0.69
Sift
Uncertain
0.0020
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.91
MutPred
0.94
Gain of disorder (P = 0.0839);Gain of disorder (P = 0.0839);
MVP
0.50
MPC
0.0069
ClinPred
0.98
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.99
gMVP
0.96

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.

Other links and lift over

dbSNP: rs149075251; hg19: chr1-219347314; API