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15-100402806-TTCTTCC-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP3BP6_ModerateBS1

The NM_001378789.1(CERS3):c.1053_1058del(p.Glu354_Glu355del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000344 in 1,613,990 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

CERS3
NM_001378789.1 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.79
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-AS1 (HGNC:51431): (CERS3 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP3
?
    BP3 - In-frame deletions/insertions in a repetitive region without a known function
Nonframeshift variant in repetitive region in NM_001378789.1
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-100402806-TTCTTCC-T is Benign according to our data. Variant chr15-100402806-TTCTTCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 722029.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00112 (171/152344) while in subpopulation AFR AF= 0.00337 (140/41586). AF 95% confidence interval is 0.00291. There are 1 homozygotes in gnomad4. There are 84 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CERS3NM_001378789.1 linkuse as main transcriptc.1053_1058del p.Glu354_Glu355del inframe_deletion 12/12 ENST00000679737.1
CERS3-AS1NR_120374.1 linkuse as main transcriptn.211+2899_211+2904del intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CERS3ENST00000679737.1 linkuse as main transcriptc.1053_1058del p.Glu354_Glu355del inframe_deletion 12/12 NM_001378789.1 P1
CERS3-AS1ENST00000560643.1 linkuse as main transcriptn.51+2899_51+2904del intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00112
AC:
171
AN:
152226
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000450
AC:
113
AN:
250848
Hom.:
1
AF XY:
0.000361
AC XY:
49
AN XY:
135586
show subpopulations
Gnomad AFR exome
AF:
0.00302
Gnomad AMR exome
AF:
0.00127
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000982
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000263
AC:
385
AN:
1461646
Hom.:
0
AF XY:
0.000237
AC XY:
172
AN XY:
727112
show subpopulations
Gnomad4 AFR exome
AF:
0.00364
Gnomad4 AMR exome
AF:
0.00114
Gnomad4 ASJ exome
AF:
0.000344
Gnomad4 EAS exome
AF:
0.000227
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000143
Gnomad4 OTH exome
AF:
0.000298
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00112
AC:
171
AN:
152344
Hom.:
1
Cov.:
33
AF XY:
0.00113
AC XY:
84
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00337
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.00122
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 18, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs541833197; hg19: chr15-100943011; API