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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024552.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS4	NM_024552.3	MANE Select	c.1096G>C	p.Ala366Pro	missense	Exon 12 of 12	NP_078828.2	Q9HA82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS4	ENST00000251363.10	TSL:1 MANE Select	c.1096G>C	p.Ala366Pro	missense	Exon 12 of 12	ENSP00000251363.5	Q9HA82
	CERS4	ENST00000559336.5	TSL:1	c.832G>C	p.Ala278Pro	missense	Exon 10 of 10	ENSP00000453815.1	H0YN04
	CERS4	ENST00000595722.5	TSL:1	n.1425G>C		non_coding_transcript_exon	Exon 13 of 13

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
PhyloP100		0.97
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs36259; hg19: chr19-8326904;