15-100456011-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378789.1(CERS3):c.881A>G(p.His294Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,612,150 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 153 hom. )

Consequence

CERS3
NM_001378789.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.15

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004370272).

BP6

Variant 15-100456011-T-C is Benign according to our data. Variant chr15-100456011-T-C is described in ClinVar as [Benign]. Clinvar id is 1178503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS3	NM_001378789.1 link	c.881A>G	p.His294Arg	missense_variant	Exon 11 of 12	ENST00000679737.1	NP_001365718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS3	ENST00000679737.1 link	c.881A>G	p.His294Arg	missense_variant	Exon 11 of 12		NM_001378789.1	ENSP00000506641.1		Q8IU89

Frequencies

GnomAD3 genomes

AF:

0.00807

AC:

1228

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00490

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0484

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0117

Gnomad SAS

AF:

0.0236

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0136

AC:

3246

AN:

238746

Hom.:

AF XY:

0.0125

AC XY:

1611

AN XY:

129282

show subpopulations

Gnomad AFR exome

AF:

0.00535

Gnomad AMR exome

AF:

0.0667

Gnomad ASJ exome

AF:

0.00137

Gnomad EAS exome

AF:

0.0105

Gnomad SAS exome

AF:

0.0243

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000979

Gnomad OTH exome

AF:

0.0143

GnomAD4 exome

AF:

0.00453

AC:

6611

AN:

1459922

Hom.:

153

Cov.:

AF XY:

0.00483

AC XY:

3506

AN XY:

726264

show subpopulations

Gnomad4 AFR exome

AF:

0.00381

Gnomad4 AMR exome

AF:

0.0610

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.0104

Gnomad4 SAS exome

AF:

0.0226

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000798

Gnomad4 OTH exome

AF:

0.00706

GnomAD4 genome

AF:

0.00818

AC:

1245

AN:

152228

Hom.:

Cov.:

AF XY:

0.00906

AC XY:

674

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00489

Gnomad4 AMR

AF:

0.0491

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0118

Gnomad4 SAS

AF:

0.0236

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00254

Hom.:

Bravo

AF:

0.0102

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.0102

AC:

1233

Asia WGS

AF:

0.0360

AC:

125

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.18

T;T;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.16

.;.;T

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.13

MPC

0.16

ClinPred

0.014

GERP RS

5.7

Varity_R

0.10

gMVP

0.24

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

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