CERS5 p.Cys75Ser

Variant names:

• chr12-50144031-C-G
• NM_147190.5:c.224G>C
• CERS5 p.Cys75Ser

Your query was ambiguous. Multiple possible variants found:

• chr12-50144031-C-G
• chr12-50144032-A-T
• chr12-50144030-AC-GG
• chr12-50144030-AC-TG
• chr12-50144030-AC-CG
• chr12-50144030-ACA-GCT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_147190.5(CERS5):​c.224G>C​(p.Cys75Ser) 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)
• Consequence: CERS5 NM_147190.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 0 publications found

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]

ENSG00000272368 (HGNC:):

ACMG classification

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=0.056369513).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS5	NM_147190.5	MANE Select	c.224G>C	p.Cys75Ser	missense	Exon 2 of 10	NP_671723.1	Q8N5B7-1
	CERS5	NM_001331070.3		c.224G>C	p.Cys75Ser	missense	Exon 2 of 11	NP_001317999.1
	CERS5	NM_001331071.3		c.224G>C	p.Cys75Ser	missense	Exon 2 of 11	NP_001318000.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS5	ENST00000317551.12	TSL:2 MANE Select	c.224G>C	p.Cys75Ser	missense	Exon 2 of 10	ENSP00000325485.6	Q8N5B7-1
	CERS5	ENST00000380189.8	TSL:1	n.224G>C		non_coding_transcript_exon	Exon 2 of 10	ENSP00000369536.4	Q49AQ3
	CERS5	ENST00000898651.1		c.224G>C	p.Cys75Ser	missense	Exon 2 of 10	ENSP00000568710.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.75
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.036	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.17	N
PhyloP100		0.064
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.76	N
REVEL	Benign	0.060
Sift	Benign	0.51	T
Sift4G	Benign	0.48	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.028
gMVP		0.22
Mutation Taster		=98/2	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-50537814;