Genetic Variant LDAH:p.Arg159Ser (chr2-20740199-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_021925.4(LDAH):c.475C>A(p.Arg159Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,457,022 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. R159H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

LDAH
NM_021925.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.92

Publications

3 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.764

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021925.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDAH	NM_021925.4	MANE Select	c.475C>A	p.Arg159Ser	missense	Exon 5 of 7	NP_068744.1	Q9H6V9-1
LDAH	NM_001282719.2		c.349C>A	p.Arg117Ser	missense	Exon 4 of 6	NP_001269648.1	A0A0A0MSH6
LDAH	NM_001282720.2		c.331C>A	p.Arg111Ser	missense	Exon 4 of 6	NP_001269649.1	Q9H6V9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDAH	ENST00000237822.8	TSL:1 MANE Select	c.475C>A	p.Arg159Ser	missense	Exon 5 of 7	ENSP00000237822.3	Q9H6V9-1
LDAH	ENST00000911673.1		c.475C>A	p.Arg159Ser	missense	Exon 5 of 8	ENSP00000581732.1
LDAH	ENST00000381090.7	TSL:5	c.475C>A	p.Arg159Ser	missense	Exon 5 of 9	ENSP00000370480.3	B5MDU6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250204

AF XY:

0.00000739

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1457022

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725138

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33366

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.00

AC:

AN:

86108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1107714

Other (OTH)

AF:

0.00

AC:

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.080

Eigen

Benign

-0.029

Eigen_PC

Benign

0.00078

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.055

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.58

PhyloP100

3.9

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.23

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.018

Polyphen

0.13

Vest4

0.37

MutPred

0.75

Gain of sheet (P = 0.1451)

MVP

0.74

MPC

0.38

ClinPred

0.93

GERP RS

5.6

Varity_R

0.57

gMVP

0.64

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over