rs281797257

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000371269.9(DHCR24):ā€‹c.881A>Cā€‹(p.Asn294Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000075 ( 0 hom. )

Consequence

DHCR24
ENST00000371269.9 missense

Scores

11
7
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.96
Variant links:
Genes affected
DHCR24 (HGNC:2859): (24-dehydrocholesterol reductase) This gene encodes a flavin adenine dinucleotide (FAD)-dependent oxidoreductase which catalyzes the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis. The protein contains a leader sequence that directs it to the endoplasmic reticulum membrane. Missense mutations in this gene have been associated with desmosterolosis. Also, reduced expression of the gene occurs in the temporal cortex of Alzheimer disease patients and overexpression has been observed in adrenal gland cancer cells. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.917

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DHCR24NM_014762.4 linkuse as main transcriptc.881A>C p.Asn294Thr missense_variant 6/9 ENST00000371269.9 NP_055577.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DHCR24ENST00000371269.9 linkuse as main transcriptc.881A>C p.Asn294Thr missense_variant 6/91 NM_014762.4 ENSP00000360316 P1Q15392-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461852
Hom.:
0
Cov.:
36
AF XY:
0.00000825
AC XY:
6
AN XY:
727228
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:
0.00000899
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.84
D;D;.;D
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.89
.;.;D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.92
D;D;D;D
MetaSVM
Pathogenic
0.84
D
MutationAssessor
Pathogenic
3.3
M;M;.;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-5.6
.;D;.;.
REVEL
Pathogenic
0.77
Sift
Uncertain
0.0010
.;D;.;.
Sift4G
Uncertain
0.0080
.;D;.;.
Polyphen
1.0
D;D;.;D
Vest4
0.86
MutPred
0.75
Loss of stability (P = 0.0776);Loss of stability (P = 0.0776);Loss of stability (P = 0.0776);Loss of stability (P = 0.0776);
MVP
0.89
MPC
1.2
ClinPred
1.0
D
GERP RS
5.2
Varity_R
0.74
gMVP
0.85

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: rs281797257; hg19: chr1-55331115; API