Variant 2-20740127-A-C 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_021925.4(LDAH):c.547T>G(p.Leu183Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

LDAH
NM_021925.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.669

Variant links:

Genes affected

LDAH (HGNC:26145): (lipid droplet associated hydrolase) Predicted to enable lipase activity. Predicted to be involved in lipid storage. Predicted to be located in endoplasmic reticulum. Predicted to be active in lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

LDAH links:

Genome browser will be placed here

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=0.26113546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDAH	NM_021925.4 linkuse as main transcript	c.547T>G	p.Leu183Val	missense_variant	5/7	ENST00000237822.8	NP_068744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDAH	ENST00000237822.8 linkuse as main transcript	c.547T>G	p.Leu183Val	missense_variant	5/7	1	NM_021925.4	ENSP00000237822	P1	Q9H6V9-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250960

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000227

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 31, 2023

The c.547T>G (p.L183V) alteration is located in exon 5 (coding exon 4) of the LDAH gene. This alteration results from a T to G substitution at nucleotide position 547, causing the leucine (L) at amino acid position 183 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

0.25

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.6

DANN

Benign

0.94

DEOGEN2

Benign

0.017

.;.;T;T;T;T;.;.;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.76

.;T;T;T;T;T;T;T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.26

T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.27

MutationTaster

Benign

1.0

D;N;N;N;N;N

PROVEAN

Benign

-1.1

.;N;.;N;N;N;.;N;N

REVEL

Benign

0.21

Sift

Benign

0.22

.;T;.;T;T;D;.;D;T

Sift4G

Benign

0.39

T;T;T;T;T;T;T;.;.

Polyphen

0.044, 0.012

.;.;.;.;B;B;.;.;.

Vest4

0.28

MutPred

0.68

.;.;.;.;Loss of catalytic residue at L183 (P = 0.0118);Loss of catalytic residue at L183 (P = 0.0118);.;.;.;

MVP

0.65

MPC

0.12

ClinPred

0.073

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.63

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