Variant 12-50143144-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_147190.5(CERS5):c.364A>C(p.Ile122Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,614,006 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 2 hom. )

Consequence

CERS5
NM_147190.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1763052).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS5	NM_147190.5 linkuse as main transcript	c.364A>C	p.Ile122Leu	missense_variant	3/10	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.364A>C	p.Ile122Leu	missense_variant	3/10	2	NM_147190.5	ENSP00000325485	P1	Q8N5B7-1
	ENST00000548468.2 linkuse as main transcript	n.106-21882T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251368

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000289

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000987

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000288

Hom.:

Bravo

AF:

0.000382

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 09, 2022

The c.364A>C (p.I122L) alteration is located in exon 3 (coding exon 3) of the CERS5 gene. This alteration results from a A to C substitution at nucleotide position 364, causing the isoleucine (I) at amino acid position 122 to be replaced by a leucine (L). 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

0.35

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

.;D;D

Eigen

Benign

0.055

Eigen_PC

Benign

0.054

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Pathogenic

0.80

MutationAssessor

Uncertain

2.2

.;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.6

N;N;.

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0080

D;D;.

Sift4G

Uncertain

0.019

D;D;.

Polyphen

0.36

.;B;.

Vest4

0.56

MVP

0.69

MPC

0.56

ClinPred

0.087

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.22

gMVP

0.68

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