12-50135790-G-A

Position:

• chr12-50135790-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_147190.5(CERS5):​c.814C>T​(p.Leu272Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CERS5 NM_147190.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.134

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31488234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS5	NM_147190.5	c.814C>T	p.Leu272Phe	missense_variant	8/10	ENST00000317551.12	NP_671723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS5	ENST00000317551.12	c.814C>T	p.Leu272Phe	missense_variant	8/10	2	NM_147190.5	ENSP00000325485	P1
	ENST00000548468.2	n.105+23489G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2022

The c.814C>T (p.L272F) alteration is located in exon 8 (coding exon 8) of the CERS5 gene. This alteration results from a C to T substitution at nucleotide position 814, causing the leucine (L) at amino acid position 272 to be replaced by a phenylalanine (F). 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	Benign	0.12
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	.;D;D
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.5	.;L;.
MutationTaster	Benign	0.50	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D;D;.
REVEL	Uncertain	0.32
Sift	Benign	0.052	T;T;.
Sift4G	Uncertain	0.039	D;D;.
Polyphen		0.095	.;B;.
Vest4		0.24
MutPred		0.53		.;Gain of catalytic residue at S277 (P = 5e-04);.;
MVP		0.85
MPC		0.44
ClinPred		0.19	T
GERP RS		1.4
Varity_R		0.088
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-50529573;