15-100455871-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001378789.1(CERS3):c.999+21del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7182 hom., cov: 0)
  • Exomes 𝑓: 0.33 (77118 hom.)
• Consequence: CERS3 NM_001378789.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.669

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-100455871-AT-A is Benign according to our data. Variant chr15-100455871-AT-A is described in ClinVar as [Benign]. Clinvar id is 1282233.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS3	NM_001378789.1	c.999+21del		intron_variant		ENST00000679737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS3	ENST00000679737.1	c.999+21del		intron_variant			NM_001378789.1	P1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45915 AN: 151900 Hom.: 7174 Cov.: 0

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.301

GnomAD3 exomes AF: 0.317 AC: 69210 AN: 217992 Hom.: 11633 AF XY: 0.328 AC XY: 38970 AN XY: 118954

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.171

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.437

Gnomad SAS exome AF: 0.417

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.310

GnomAD4 exome AF: 0.328 AC: 458141 AN: 1394822 Hom.: 77118 Cov.: 0 AF XY: 0.331 AC XY: 229707 AN XY: 693224

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.408

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.334

GnomAD4 genome AF: 0.302 AC: 45949 AN: 152018 Hom.: 7182 Cov.: 0 AF XY: 0.303 AC XY: 22504 AN XY: 74318

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.306

Alfa AF: 0.212 Hom.: 692

Bravo AF: 0.293

Asia WGS AF: 0.412 AC: 1431 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs11323964; hg19: chr15-100996076;