chr19-8261982-C-G

Position:

• chr19-8261982-C-G

Variant summary

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

The NM_024552.3(CERS4):​c.1058C>G​(p.Ala353Gly) 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. 15/21 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. A353V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CERS4 NM_024552.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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=0.072145104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS4	NM_024552.3	c.1058C>G	p.Ala353Gly	missense_variant	12/12	ENST00000251363.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS4	ENST00000251363.10	c.1058C>G	p.Ala353Gly	missense_variant	12/12	1	NM_024552.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.8
DANN	Benign	0.75
DEOGEN2	Benign	0.087	T;T;T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.20	T;.;T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.072	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.17	N;N;N;N
Sift	Benign	0.32	T;T;T;T
Sift4G	Benign	0.38	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.099
MutPred		0.14		.;Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);.;
MVP		0.095
MPC		0.061
ClinPred		0.071	T
GERP RS		3.0
Varity_R		0.017
gMVP		0.22

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: rs17160348; hg19: chr19-8326866;