NM_147190.5:c.223T>C

Variant names:

• chr12-50144032-A-G
• rs7302981
• NM_147190.5:c.223T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_147190.5(CERS5):​c.223T>C​(p.Cys75Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 1,608,360 control chromosomes in the GnomAD database, including 354,129 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.72 (40209 hom., cov: 32)
  • Exomes 𝑓: 0.65 (313920 hom.)
• Consequence: CERS5 NM_147190.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541
• Publications: 76 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.035129E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS5	NM_147190.5	MANE Select	c.223T>C	p.Cys75Arg	missense	Exon 2 of 10	NP_671723.1
	CERS5	NM_001331070.3		c.223T>C	p.Cys75Arg	missense	Exon 2 of 11	NP_001317999.1
	CERS5	NM_001331071.3		c.223T>C	p.Cys75Arg	missense	Exon 2 of 11	NP_001318000.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS5	ENST00000317551.12	TSL:2 MANE Select	c.223T>C	p.Cys75Arg	missense	Exon 2 of 10	ENSP00000325485.6
	CERS5	ENST00000380189.8	TSL:1	n.223T>C		non_coding_transcript_exon	Exon 2 of 10	ENSP00000369536.4
	CERS5	ENST00000422340.6	TSL:2	c.49T>C	p.Cys17Arg	missense	Exon 3 of 11	ENSP00000389050.2

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108723 AN: 151996 Hom.: 40155 Cov.: 32

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.683

GnomAD2 exomes AF: 0.693 AC: 174107 AN: 251416 AF XY: 0.688

Gnomad AFR exome AF: 0.887

Gnomad AMR exome AF: 0.750

Gnomad ASJ exome AF: 0.524

Gnomad EAS exome AF: 0.920

Gnomad FIN exome AF: 0.617

Gnomad NFE exome AF: 0.622

Gnomad OTH exome AF: 0.669

GnomAD4 exome AF: 0.651 AC: 948607 AN: 1456246 Hom.: 313920 Cov.: 32 AF XY: 0.653 AC XY: 473322 AN XY: 724806

African (AFR) AF: 0.889 AC: 29671 AN: 33384

American (AMR) AF: 0.746 AC: 33372 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 13689 AN: 26092

East Asian (EAS) AF: 0.929 AC: 36866 AN: 39690

South Asian (SAS) AF: 0.762 AC: 65590 AN: 86130

European-Finnish (FIN) AF: 0.620 AC: 33116 AN: 53388

Middle Eastern (MID) AF: 0.601 AC: 3467 AN: 5766

European-Non Finnish (NFE) AF: 0.626 AC: 692812 AN: 1106878

Other (OTH) AF: 0.665 AC: 40024 AN: 60208

GnomAD4 genome AF: 0.715 AC: 108833 AN: 152114 Hom.: 40209 Cov.: 32 AF XY: 0.717 AC XY: 53286 AN XY: 74368

African (AFR) AF: 0.883 AC: 36663 AN: 41520

American (AMR) AF: 0.715 AC: 10916 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1816 AN: 3468

East Asian (EAS) AF: 0.920 AC: 4771 AN: 5186

South Asian (SAS) AF: 0.779 AC: 3751 AN: 4816

European-Finnish (FIN) AF: 0.609 AC: 6424 AN: 10552

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42377 AN: 67984

Other (OTH) AF: 0.682 AC: 1438 AN: 2108

Alfa AF: 0.648 Hom.: 154399

Bravo AF: 0.729

TwinsUK AF: 0.628 AC: 2327

ALSPAC AF: 0.622 AC: 2397

ESP6500AA AF: 0.878 AC: 3869

ESP6500EA AF: 0.619 AC: 5324

ExAC AF: 0.699 AC: 84815

Asia WGS AF: 0.835 AC: 2903 AN: 3478

EpiCase AF: 0.613

EpiControl AF: 0.614

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.74
DEOGEN2	Benign	0.086	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.0062	T
MetaRNN	Benign	6.0e-7	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.54
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.16
Sift	Benign	0.41	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.065
MPC		0.62
ClinPred		0.00088	T
GERP RS		3.1
Varity_R		0.097
gMVP		0.37
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7302981; hg19: chr12-50537815; COSMIC: COSV107363633; COSMIC: COSV107363633;