15-100402638-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378789.1(CERS3):c.*75C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,438,272 control chromosomes in the GnomAD database, including 247,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (24719 hom., cov: 32)
  • Exomes 𝑓: 0.59 (222334 hom.)
• Consequence: CERS3 NM_001378789.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.104

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)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 15-100402638-G-T is Benign according to our data. Variant chr15-100402638-G-T is described in ClinVar as [Benign]. Clinvar id is 1209729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS3	NM_001378789.1	c.*75C>A		3_prime_UTR_variant	12/12	ENST00000679737.1
CERS3-AS1	NR_120374.1	n.211+2713G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS3	ENST00000679737.1	c.*75C>A		3_prime_UTR_variant	12/12		NM_001378789.1	P1
CERS3-AS1	ENST00000560643.1	n.51+2713G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86239 AN: 151976 Hom.: 24718 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.590

GnomAD4 exome AF: 0.586 AC: 753329 AN: 1286178 Hom.: 222334 Cov.: 17 AF XY: 0.585 AC XY: 373720 AN XY: 639206

Gnomad4 AFR exome AF: 0.542

Gnomad4 AMR exome AF: 0.499

Gnomad4 ASJ exome AF: 0.581

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.530

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.601

Gnomad4 OTH exome AF: 0.578

GnomAD4 genome AF: 0.567 AC: 86280 AN: 152094 Hom.: 24719 Cov.: 32 AF XY: 0.563 AC XY: 41831 AN XY: 74328

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.589

Alfa AF: 0.559 Hom.: 8148

Bravo AF: 0.565

Asia WGS AF: 0.498 AC: 1731 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive congenital ichthyosis 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.9
Dann	Benign	0.74

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: rs1023782; hg19: chr15-100942843; COSMIC: COSV52575070;