chr11-76926636-G-T

Variant names:

• chr11-76926636-G-T
• rs4479014
• NM_018367.7:c.183G>T

Variant summary

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

The NM_018367.7(ACER3):​c.183G>T​(p.Lys61Asn) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACER3 NM_018367.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

Genes affected

ACER3 (HGNC:16066): (alkaline ceramidase 3) Enables N-acylsphingosine amidohydrolase activity and metal ion binding activity. Involved in several processes, including myelination; positive regulation of cell population proliferation; and sphingolipid metabolic process. Is integral component of Golgi membrane and integral component of endoplasmic reticulum membrane. Biomarker of hepatocellular carcinoma and non-alcoholic steatohepatitis. [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=0.23502487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACER3	NM_018367.7	c.183G>T	p.Lys61Asn	missense_variant	Exon 2 of 11	ENST00000532485.6	NP_060837.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACER3	ENST00000532485.6	c.183G>T	p.Lys61Asn	missense_variant	Exon 2 of 11	1	NM_018367.7	ENSP00000434480.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.94	N;N
REVEL	Benign	0.084
Sift	Benign	0.33	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.64	.;P
Vest4		0.69
MutPred		0.51		.;Loss of methylation at K61 (P = 0.0137);
MVP		0.39
MPC		1.0
ClinPred		0.82	D
GERP RS		1.6
Varity_R		0.42
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4479014; hg19: chr11-76637680;