Variant 15-100402839-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001378789.1(CERS3):c.1026C>T(p.Asp342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 1,608,880 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0086 ( 24 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 144 hom. )

Consequence

CERS3
NM_001378789.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.535

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 15-100402839-G-A is Benign according to our data. Variant chr15-100402839-G-A is described in ClinVar as [Benign]. Clinvar id is 2018095.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.535 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS3	NM_001378789.1 linkuse as main transcript	c.1026C>T	p.Asp342=	synonymous_variant	12/12	ENST00000679737.1
CERS3-AS1	NR_120374.1 linkuse as main transcript	n.211+2914G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS3	ENST00000679737.1 linkuse as main transcript	c.1026C>T	p.Asp342=	synonymous_variant	12/12		NM_001378789.1	P1
CERS3-AS1	ENST00000560643.1 linkuse as main transcript	n.51+2914G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00850

AC:

1292

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00578

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0492

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00926

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00163

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.0134

AC:

3210

AN:

239514

Hom.:

AF XY:

0.0123

AC XY:

1595

AN XY:

129310

show subpopulations

Gnomad AFR exome

AF:

0.00607

Gnomad AMR exome

AF:

0.0620

Gnomad ASJ exome

AF:

0.000713

Gnomad EAS exome

AF:

0.00756

Gnomad SAS exome

AF:

0.0221

Gnomad FIN exome

AF:

0.0000962

Gnomad NFE exome

AF:

0.00161

Gnomad OTH exome

AF:

0.0147

GnomAD4 exome

AF:

0.00481

AC:

7012

AN:

1456742

Hom.:

144

Cov.:

AF XY:

0.00510

AC XY:

3697

AN XY:

724254

show subpopulations

Gnomad4 AFR exome

AF:

0.00545

Gnomad4 AMR exome

AF:

0.0614

Gnomad4 ASJ exome

AF:

0.000538

Gnomad4 EAS exome

AF:

0.00871

Gnomad4 SAS exome

AF:

0.0221

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.00663

GnomAD4 genome

AF:

0.00862

AC:

1312

AN:

152138

Hom.:

Cov.:

AF XY:

0.00949

AC XY:

706

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00581

Gnomad4 AMR

AF:

0.0499

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00928

Gnomad4 SAS

AF:

0.0230

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00163

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00323

Hom.:

Bravo

AF:

0.0109

Asia WGS

AF:

0.0290

AC:

100

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

Cadd

Benign

1.4

Dann

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

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