dbSNP rs7302981: CERS5:p.Cys75Gly (chr12-50144032-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_147190.5(CERS5):c.223T>G(p.Cys75Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CERS5
NM_147190.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.541

Publications

76 publications found

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:

ENSG00000272368 (HGNC:):

ENSG00000272368 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045167714).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147190.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CERS5	NM_147190.5	MANE Select	c.223T>G	p.Cys75Gly	missense	Exon 2 of 10	NP_671723.1
CERS5	NM_001331070.3		c.223T>G	p.Cys75Gly	missense	Exon 2 of 11	NP_001317999.1
CERS5	NM_001331071.3		c.223T>G	p.Cys75Gly	missense	Exon 2 of 11	NP_001318000.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CERS5	ENST00000317551.12	TSL:2 MANE Select	c.223T>G	p.Cys75Gly	missense	Exon 2 of 10	ENSP00000325485.6
CERS5	ENST00000380189.8	TSL:1	n.223T>G		non_coding_transcript_exon	Exon 2 of 10	ENSP00000369536.4
CERS5	ENST00000422340.6	TSL:2	c.49T>G	p.Cys17Gly	missense	Exon 3 of 11	ENSP00000389050.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1459340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726232

African (AFR)

AF:

0.00

AC:

AN:

33414

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109710

Other (OTH)

AF:

0.00

AC:

AN:

60308

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.097

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.023

M_CAP

Benign

0.014

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.090

PhyloP100

0.54

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.16

REVEL

Benign

0.12

Sift

Benign

0.36

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.095

MutPred

0.47

Gain of catalytic residue at P71 (P = 0)

MVP

0.41

MPC

0.43

ClinPred

0.17

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.039

gMVP

0.26

Mutation Taster

=97/3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over