19-8256648-C-G

Position:

• chr19-8256648-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024552.3(CERS4):​c.550C>G​(p.Leu184Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CERS4 NM_024552.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.798

Genes affected

CERS4 (HGNC:23747): (ceramide synthase 4) Enables sphingosine N-acyltransferase activity. Involved in ceramide biosynthetic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

CERS4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS4	NM_024552.3	c.550C>G	p.Leu184Val	missense_variant	8/12	ENST00000251363.10	NP_078828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS4	ENST00000251363.10	c.550C>G	p.Leu184Val	missense_variant	8/12	1	NM_024552.3	ENSP00000251363.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Dec 26, 2023

The c.550C>G (p.L184V) alteration is located in exon 8 (coding exon 6) of the CERS4 gene. This alteration results from a C to G substitution at nucleotide position 550, causing the leucine (L) at amino acid position 184 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.49	T;T;T;D;.
Eigen	Benign	-0.018
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.86	D;.;T;T;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.56	D;D;D;D;D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Uncertain	2.4	.;M;M;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.8	N;N;N;N;N
REVEL	Uncertain	0.51
Sift	Benign	0.18	T;T;T;T;T
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.99	.;D;D;.;.
Vest4		0.42
MutPred		0.65		.;Gain of MoRF binding (P = 0.5442);Gain of MoRF binding (P = 0.5442);Gain of MoRF binding (P = 0.5442);Gain of MoRF binding (P = 0.5442);
MVP		0.59
MPC		0.30
ClinPred		0.71	D
GERP RS		2.0
Varity_R		0.28
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: -5

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: chr19-8321532;