11-76926607-G-T

Variant names:

• chr11-76926607-G-T
• rs4379869
• NM_018367.7:c.154G>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.154G>T​(p.Val52Phe) 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. 14/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACER3 NM_018367.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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=0.15089837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACER3	NM_018367.7	c.154G>T	p.Val52Phe	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.154G>T	p.Val52Phe	missense_variant	Exon 2 of 11	1	NM_018367.7	ENSP00000434480.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456054 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 724728

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	.;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.31	T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.92	N;N
REVEL	Benign	0.15
Sift	Benign	0.076	T;T
Sift4G	Benign	0.62	T;T
Polyphen		0.012	.;B
Vest4		0.43
MutPred		0.57		.;Loss of catalytic residue at V52 (P = 0.0349);
MVP		0.58
MPC		0.89
ClinPred		0.33	T
GERP RS		2.1
Varity_R		0.11
gMVP		0.34

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: rs4379869; hg19: chr11-76637651;