Variant 2-20790375-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021925.4(LDAH):c.178T>C(p.Tyr60His) variant causes a missense change. The variant allele was found at a frequency of 0.000464 in 1,613,304 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 0 hom. )

Consequence

LDAH
NM_021925.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDAH	NM_021925.4 linkuse as main transcript	c.178T>C	p.Tyr60His	missense_variant	3/7	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.178T>C	p.Tyr60His	missense_variant	3/7	1	NM_021925.4	ENSP00000237822	P1	Q9H6V9-1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.000559

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000396

AC:

AN:

250210

Hom.:

AF XY:

0.000444

AC XY:

AN XY:

135210

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000840

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000485

AC:

708

AN:

1461074

Hom.:

Cov.:

AF XY:

0.000447

AC XY:

325

AN XY:

726768

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000621

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000269

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.000559

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000686

Hom.:

Bravo

AF:

0.000283

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000469

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000474

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

May 06, 2024

The c.178T>C (p.Y60H) alteration is located in exon 3 (coding exon 2) of the LDAH gene. This alteration results from a T to C substitution at nucleotide position 178, causing the tyrosine (Y) at amino acid position 60 to be replaced by a histidine (H). 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

0.61

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

T;T;T;.;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.87

D;D;D;D;D

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.62

D;D;D;D;D

MetaSVM

Uncertain

0.081

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PROVEAN

Pathogenic

-4.6

D;D;D;D;D

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;D;D;.;.

Vest4

0.86

MVP

0.52

MPC

0.57

ClinPred

0.50

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.95

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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