15-100455661-A-T

Position:

• chr15-100455661-A-T

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+232T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,130 control chromosomes in the GnomAD database, including 3,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3322 hom., cov: 33)
• Consequence: CERS3 NM_001378789.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65

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=-0.97).
• BP6: Variant 15-100455661-A-T is Benign according to our data. Variant chr15-100455661-A-T is described in ClinVar as [Benign]. Clinvar id is 1269421.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS3	NM_001378789.1	c.999+232T>A		intron_variant		ENST00000679737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS3	ENST00000679737.1	c.999+232T>A		intron_variant			NM_001378789.1	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29260 AN: 152010 Hom.: 3296 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.193 AC: 29343 AN: 152130 Hom.: 3322 Cov.: 33 AF XY: 0.196 AC XY: 14546 AN XY: 74402

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.157

Alfa AF: 0.0804 Hom.: 94

Bravo AF: 0.206

Asia WGS AF: 0.179 AC: 624 AN: 3464

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

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.068
DANN	Benign	0.20

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: rs12592841; hg19: chr15-100995866;