chr19-8261982-C-A

Variant names:

• chr19-8261982-C-A
• rs17160348
• NM_024552.3:c.1058C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024552.3(CERS4):​c.1058C>A​(p.Ala353Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000553 in 1,445,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CERS4 NM_024552.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 24 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037539423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS4	NM_024552.3	c.1058C>A	p.Ala353Glu	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.1058C>A	p.Ala353Glu	missense_variant	Exon 12 of 12	1	NM_024552.3	ENSP00000251363.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000127 AC: 3 AN: 236862 AF XY: 0.00000779

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000111

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000922

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000553 AC: 8 AN: 1445550 Hom.: 0 Cov.: 31 AF XY: 0.00000696 AC XY: 5 AN XY: 718106

African (AFR) AF: 0.00 AC: 0 AN: 32710

American (AMR) AF: 0.00 AC: 0 AN: 41130

Ashkenazi Jewish (ASJ) AF: 0.0000396 AC: 1 AN: 25232

East Asian (EAS) AF: 0.00 AC: 0 AN: 39524

South Asian (SAS) AF: 0.0000356 AC: 3 AN: 84224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00000362 AC: 4 AN: 1104436

Other (OTH) AF: 0.00 AC: 0 AN: 59614

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 8288

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.8
DANN	Benign	0.25
DEOGEN2	Benign	0.083	T;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.18	T;.;T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.038	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.8	.;N;N;.
PhyloP100		1.1
PrimateAI	Benign	0.41	T
PROVEAN	Benign	3.0	N;N;N;N
REVEL	Benign	0.060
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.14
MutPred		0.19		.;Loss of loop (P = 0.0153);Loss of loop (P = 0.0153);.;
MVP		0.055
MPC		0.060
ClinPred		0.021	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.25
Mutation Taster		=96/4	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: rs17160348; hg19: chr19-8326866; COSMIC: COSV52166325; COSMIC: COSV52166325;