ENST00000284382.8:c.-355+2793T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000284382.8(CERS3):​c.-355+2793T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,832 control chromosomes in the GnomAD database, including 19,249 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 19249 hom., cov: 33)

Consequence

CERS3
ENST00000284382.8 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.823

Publications

5 publications found
Variant links:
Genes affected
CERS3 (HGNC:23752): (ceramide synthase 3) This gene is a member of the ceramide synthase family of genes. The ceramide synthase enzymes regulate sphingolipid synthesis by catalyzing the formation of ceramides from sphingoid base and acyl-coA substrates. This family member is involved in the synthesis of ceramides with ultra-long-chain acyl moieties (ULC-Cers), important to the epidermis in its role in creating a protective barrier from the environment. The protein encoded by this gene has also been implicated in modification of the lipid structures required for spermatogenesis. Mutations in this gene have been associated with male fertility defects, and epidermal defects, including ichthyosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
CERS3 Gene-Disease associations (from GenCC):
  • autosomal recessive congenital ichthyosis 9
    Inheritance: AR Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
  • congenital non-bullous ichthyosiform erythroderma
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CERS3NM_001290341.2 linkc.-461+2358T>G intron_variant Intron 1 of 13 NP_001277270.1 Q8IU89
CERS3NM_001290342.2 linkc.-355+2266T>G intron_variant Intron 1 of 12 NP_001277271.1 Q8IU89
CERS3NM_001290343.2 linkc.-355+2789T>G intron_variant Intron 1 of 12 NP_001277272.1 Q8IU89

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CERS3ENST00000284382.8 linkc.-355+2793T>G intron_variant Intron 1 of 12 1 ENSP00000284382.4 Q8IU89
CERS3ENST00000394113.5 linkc.-494+2358T>G intron_variant Intron 1 of 13 1 ENSP00000377672.3 Q8IU89
CERS3ENST00000538112.6 linkc.-355+2266T>G intron_variant Intron 1 of 12 1 ENSP00000437640.2 Q8IU89

Frequencies

GnomAD3 genomes
AF:
0.500
AC:
75801
AN:
151712
Hom.:
19233
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.437
Gnomad AMI
AF:
0.486
Gnomad AMR
AF:
0.574
Gnomad ASJ
AF:
0.451
Gnomad EAS
AF:
0.304
Gnomad SAS
AF:
0.597
Gnomad FIN
AF:
0.587
Gnomad MID
AF:
0.475
Gnomad NFE
AF:
0.518
Gnomad OTH
AF:
0.501
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.500
AC:
75865
AN:
151832
Hom.:
19249
Cov.:
33
AF XY:
0.505
AC XY:
37504
AN XY:
74196
show subpopulations
African (AFR)
AF:
0.437
AC:
18103
AN:
41420
American (AMR)
AF:
0.575
AC:
8762
AN:
15246
Ashkenazi Jewish (ASJ)
AF:
0.451
AC:
1563
AN:
3466
East Asian (EAS)
AF:
0.304
AC:
1575
AN:
5178
South Asian (SAS)
AF:
0.595
AC:
2866
AN:
4814
European-Finnish (FIN)
AF:
0.587
AC:
6173
AN:
10522
Middle Eastern (MID)
AF:
0.463
AC:
136
AN:
294
European-Non Finnish (NFE)
AF:
0.518
AC:
35193
AN:
67880
Other (OTH)
AF:
0.500
AC:
1056
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
1923
3845
5768
7690
9613
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
684
1368
2052
2736
3420
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.510
Hom.:
4608
Bravo
AF:
0.491
Asia WGS
AF:
0.475
AC:
1650
AN:
3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
1.4
DANN
Benign
0.52
PhyloP100
-0.82
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12438080; hg19: chr15-101082063; API