Variant 15-100402806-TTCTTCC-T details in Genebe, Genetics Data Aggregator

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 links:

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

CERS3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_001378789.1

BP6

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

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	Protein	UniProt
CERS3	NM_001378789.1 linkuse as main transcript	c.1053_1058del	p.Glu354_Glu355del	inframe_deletion	12/12	ENST00000679737.1	NP_001365718.1
CERS3-AS1	NR_120374.1 linkuse as main transcript	n.211+2899_211+2904del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS3	ENST00000679737.1 linkuse as main transcript	c.1053_1058del	p.Glu354_Glu355del	inframe_deletion	12/12		NM_001378789.1	ENSP00000506641	P1
CERS3-AS1	ENST00000560643.1 linkuse as main transcript	n.51+2899_51+2904del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

171

AN:

152226

Hom.:

Cov.:

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.:

AF XY:

0.000361

AC XY:

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.:

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

AF:

0.00112

AC:

171

AN:

152344

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

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:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over