rs759773695

Variant summary

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

The NM_021925.4(LDAH):​c.221G>C​(p.Arg74Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R74C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

LDAH
NM_021925.4 missense

Scores

1
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0140
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]

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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 rank MANE Protein UniProt
LDAHNM_021925.4 linkc.221G>C p.Arg74Pro missense_variant Exon 3 of 7 ENST00000237822.8 NP_068744.1 Q9H6V9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LDAHENST00000237822.8 linkc.221G>C p.Arg74Pro missense_variant Exon 3 of 7 1 NM_021925.4 ENSP00000237822.3 Q9H6V9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461764
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727194
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.66
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.072
T;T;T;.;.
Eigen
Benign
0.043
Eigen_PC
Benign
-0.00095
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.82
T;T;T;T;T
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.46
T;T;T;T;T
MetaSVM
Benign
-0.64
T
PROVEAN
Uncertain
-2.8
D;D;D;D;D
REVEL
Uncertain
0.32
Sift
Benign
0.030
D;D;D;D;D
Sift4G
Uncertain
0.059
T;T;T;D;D
Polyphen
0.99
D;B;B;.;.
Vest4
0.60
MutPred
0.54
Loss of catalytic residue at R74 (P = 0.0256);Loss of catalytic residue at R74 (P = 0.0256);Loss of catalytic residue at R74 (P = 0.0256);.;Loss of catalytic residue at R74 (P = 0.0256);
MVP
0.47
MPC
0.56
ClinPred
0.97
D
GERP RS
2.9
Varity_R
0.74
gMVP
0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-20990092; API