NM_021267.5:c.164T>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_021267.5(CERS1):c.164T>A(p.Leu55Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,249,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

CERS1
NM_021267.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.34

Publications

0 publications found

Variant links:

Genes affected

CERS1 (HGNC:14253): (ceramide synthase 1) This gene encodes a ceramide synthase enzyme, which catalyzes the synthesis of ceramide, the hydrophobic moiety of sphingolipids. The encoded enzyme synthesizes 18-carbon (C18) ceramide in brain neurons. Elevated expression of this gene may be associated with increased longevity, while decreased expression of this gene may be associated with myoclonus epilepsy with dementia in human patients. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1. [provided by RefSeq, Jul 2016]

CERS1 links:

GDF1 (HGNC:4214): (growth differentiation factor 1) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. Studies in rodents suggest that this protein is involved in the establishment of left-right asymmetry in early embryogenesis and in neural development in later embryogenesis. The encoded protein is translated from a bicistronic mRNA that also encodes ceramide synthase 1. Mutations in this gene are associated with several congenital cardiovascular malformations. [provided by RefSeq, Jul 2016]

GDF1 Gene-Disease associations (from GenCC):

right atrial isomerism
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
congenital heart defects, multiple types, 6
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Illumina, Ambry Genetics
conotruncal heart malformations
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

GDF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.4152677).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021267.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CERS1	NM_021267.5	MANE Select	c.164T>A	p.Leu55Gln	missense	Exon 1 of 8	NP_067090.1	P27544-1
GDF1	NM_001492.6	MANE Select	c.-1159T>A		5_prime_UTR	Exon 1 of 8	NP_001483.3
CERS1	NM_001387439.1		c.164T>A	p.Leu55Gln	missense	Exon 1 of 7	NP_001374368.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CERS1	ENST00000623882.4	TSL:1 MANE Select	c.164T>A	p.Leu55Gln	missense	Exon 1 of 8	ENSP00000485308.1	P27544-1
CERS1	ENST00000429504.6	TSL:1	c.164T>A	p.Leu55Gln	missense	Exon 1 of 6	ENSP00000389044.1	P27544-2
GDF1	ENST00000247005.8	TSL:1 MANE Select	c.-1159T>A		5_prime_UTR	Exon 1 of 8	ENSP00000247005.5	P27539

Frequencies

GnomAD3 genomes

AF:

0.0000800

AC:

AN:

149990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000178

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000267

AC:

294

AN:

1099836

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

139

AN XY:

533702

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20902

American (AMR)

AF:

0.00

AC:

AN:

8550

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12894

East Asian (EAS)

AF:

0.00

AC:

AN:

22020

South Asian (SAS)

AF:

0.00

AC:

AN:

39588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2768

European-Non Finnish (NFE)

AF:

0.000312

AC:

290

AN:

928544

Other (OTH)

AF:

0.0000944

AC:

AN:

42358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000800

AC:

AN:

149990

Hom.:

Cov.:

AF XY:

0.0000546

AC XY:

AN XY:

73198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41132

American (AMR)

AF:

0.00

AC:

AN:

15086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000178

AC:

AN:

67324

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000982

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Progressive myoclonic epilepsy type 8 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.57

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.42

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

2.3

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.14

Sift

Uncertain

0.011

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.38

MutPred

0.40

Gain of solvent accessibility (P = 0.0044)

MVP

0.52

ClinPred

0.95

GERP RS

2.7

PromoterAI

0.53

Over-expression

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.50

Mutation Taster

=71/29

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over