Variant 12-50135993-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_147190.5(CERS5):c.713G>A(p.Arg238Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 1,369,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

CERS5
NM_147190.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

CERS5 (HGNC:23749): (ceramide synthase 5) This gene encodes a protein that belongs to the TLC (TRAM, LAG1 and CLN8 homology domains) family of proteins. The encoded protein functions in the synthesis of ceramide, a lipid molecule that is involved in a several cellular signaling pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

CERS5 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS5	NM_147190.5 linkuse as main transcript	c.713G>A	p.Arg238Gln	missense_variant	7/10	ENST00000317551.12	NP_671723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS5	ENST00000317551.12 linkuse as main transcript	c.713G>A	p.Arg238Gln	missense_variant	7/10	2	NM_147190.5	ENSP00000325485	P1	Q8N5B7-1
	ENST00000548468.2 linkuse as main transcript	n.105+23692C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000113

AC:

AN:

177494

Hom.:

AF XY:

0.0000215

AC XY:

AN XY:

93190

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000634

Gnomad SAS exome

AF:

0.0000701

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000657

AC:

AN:

1369954

Hom.:

Cov.:

AF XY:

0.0000104

AC XY:

AN XY:

672628

show subpopulations

Gnomad4 AFR exome

AF:

0.0000660

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000768

Gnomad4 SAS exome

AF:

0.0000145

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000280

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000170

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2023

The c.713G>A (p.R238Q) alteration is located in exon 7 (coding exon 7) of the CERS5 gene. This alteration results from a G to A substitution at nucleotide position 713, causing the arginine (R) at amino acid position 238 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.87

.;D;D

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.93

D;D;D

MetaSVM

Pathogenic

0.91

MutationAssessor

Pathogenic

3.8

.;H;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-4.0

D;D;.

REVEL

Pathogenic

0.88

Sift

Uncertain

0.0020

D;D;.

Sift4G

Uncertain

0.0030

D;D;.

Polyphen

1.0

.;D;.

Vest4

0.86

MutPred

0.79

.;Gain of catalytic residue at R238 (P = 0.0045);.;

MVP

0.89

MPC

1.2

ClinPred

0.99

GERP RS

4.3

Varity_R

0.64

gMVP

0.88

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