19-8262060-G-C

Position:

• chr19-8262060-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000251363.10(CERS4):​c.1136G>C​(p.Arg379Pro) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R379Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CERS4 ENST00000251363.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26364902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS4	NM_024552.3	c.1136G>C	p.Arg379Pro	missense_variant	12/12	ENST00000251363.10	NP_078828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS4	ENST00000251363.10	c.1136G>C	p.Arg379Pro	missense_variant	12/12	1	NM_024552.3	ENSP00000251363	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;T;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.063
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.81	T;.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	2.0	.;M;M;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Uncertain	0.046	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.32
MutPred		0.24		.;Loss of MoRF binding (P = 0.0094);Loss of MoRF binding (P = 0.0094);.;
MVP		0.48
MPC		0.41
ClinPred		0.80	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.46
gMVP		0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs17160349; hg19: chr19-8326944;