19-8262020-G-C

Variant names:

• chr19-8262020-G-C
• rs36259
• NM_024552.3:c.1096G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024552.3(CERS4):​c.1096G>C​(p.Ala366Pro) 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. 15/22 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: 35)
• Consequence: CERS4 NM_024552.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.970
• Publications: 43 publications found

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]

ENSG00000303688 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091602206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS4	NM_024552.3	c.1096G>C	p.Ala366Pro	missense_variant	Exon 12 of 12	ENST00000251363.10	NP_078828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS4	ENST00000251363.10	c.1096G>C	p.Ala366Pro	missense_variant	Exon 12 of 12	1	NM_024552.3	ENSP00000251363.5

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 138012

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.5
DANN	Benign	0.95
DEOGEN2	Benign	0.098	T;T;T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.67	T;.;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.092	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L;L;.
PhyloP100		0.97
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.89	N;N;N;N
REVEL	Benign	0.082
Sift	Benign	0.30	T;T;T;D
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.70	.;P;P;.
Vest4		0.15
MutPred		0.15		.;Loss of stability (P = 0.119);Loss of stability (P = 0.119);.;
MVP		0.16
MPC		0.15
ClinPred		0.28	T
GERP RS		0.91
Varity_R		0.15
gMVP		0.23
Mutation Taster		=94/6	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

Other links and lift over

dbSNP: rs36259; hg19: chr19-8326904;