11-77026201-A-T

Variant names:

• chr11-77026201-A-T
• rs1945085
• NM_018367.7:c.*5874A>T

Variant summary

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

The NM_018367.7(ACER3):​c.*5874A>T variant causes a 3 prime UTR 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. 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 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 4 publications found

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]

ACER3 Gene-Disease associations (from GenCC):

• alkaline ceramidase 3 deficiency

  Inheritance: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACER3-AS1 (HGNC:58067):

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 (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018367.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACER3	NM_018367.7	MANE Select	c.*5874A>T		3_prime_UTR	Exon 11 of 11	NP_060837.3
	ACER3	NM_001300953.2		c.*5874A>T		3_prime_UTR	Exon 10 of 10	NP_001287882.1
	ACER3	NM_001300954.2		c.*5874A>T		3_prime_UTR	Exon 11 of 11	NP_001287883.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACER3	ENST00000532485.6	TSL:1 MANE Select	c.*5874A>T		3_prime_UTR	Exon 11 of 11	ENSP00000434480.1
	ACER3-AS1	ENST00000804914.1		n.117+9367T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 10779

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.51
PhyloP100		1.6

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: rs1945085; hg19: chr11-76737245;