15-100455720-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378789.1(CERS3):c.999+173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,940 control chromosomes in the GnomAD database, including 18,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (18763 hom., cov: 32)
• Consequence: CERS3 NM_001378789.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.37

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 15-100455720-A-G is Benign according to our data. Variant chr15-100455720-A-G is described in ClinVar as [Benign]. Clinvar id is 1221617.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS3	NM_001378789.1	c.999+173T>C		intron_variant		ENST00000679737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS3	ENST00000679737.1	c.999+173T>C		intron_variant			NM_001378789.1	P1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74791 AN: 151822 Hom.: 18773 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.533

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.492 AC: 74791 AN: 151940 Hom.: 18763 Cov.: 32 AF XY: 0.489 AC XY: 36335 AN XY: 74274

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.527

Alfa AF: 0.498 Hom.: 3008

Bravo AF: 0.487

Asia WGS AF: 0.408 AC: 1414 AN: 3470

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	14
Dann	Benign	0.91

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: rs12050655; hg19: chr15-100995925; COSMIC: COSV52573362;