11-76990562-G-T

Variant names:

• chr11-76990562-G-T
• rs3740767
• NM_018367.7:c.426G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018367.7(ACER3):​c.426G>T​(p.Pro142Pro) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. P142P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACER3 NM_018367.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 27 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=0.117 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACER3	NM_018367.7	MANE Select	c.426G>T	p.Pro142Pro	synonymous	Exon 6 of 11	NP_060837.3
	ACER3	NM_001300953.2		c.315G>T	p.Pro105Pro	synonymous	Exon 5 of 10	NP_001287882.1	B7Z2Q2
	ACER3	NM_001300954.2		c.141G>T	p.Pro47Pro	synonymous	Exon 6 of 11	NP_001287883.1	B7Z2V2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACER3	ENST00000532485.6	TSL:1 MANE Select	c.426G>T	p.Pro142Pro	synonymous	Exon 6 of 11	ENSP00000434480.1	Q9NUN7-1
	ACER3	ENST00000278544.9	TSL:1	n.*266G>T		non_coding_transcript_exon	Exon 6 of 11	ENSP00000278544.5	J3KN85
	ACER3	ENST00000525194.5	TSL:1	n.*378G>T		non_coding_transcript_exon	Exon 7 of 11	ENSP00000432109.1	E9PKR3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.1
DANN	Benign	0.67
PhyloP100		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs3740767; hg19: chr11-76701606;