Genetic Variant NM_001129.5:c.185_186delCC (chr7-44104848-GCC-G) – ACMG Classification: Pathogenic (12 pts)

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001129.5(AEBP1):c.185_186delCC(p.Pro62HisfsTer75) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

AEBP1
NM_001129.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.01

Variant links:

Genes affected

AEBP1 (HGNC:303): (AE binding protein 1) This gene encodes a member of carboxypeptidase A protein family. The encoded protein may function as a transcriptional repressor and play a role in adipogenesis and smooth muscle cell differentiation. Studies in mice suggest that this gene functions in wound healing and abdominal wall development. Overexpression of this gene is associated with glioblastoma. [provided by RefSeq, May 2013]

AEBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 7-44104848-GCC-G is Pathogenic according to our data. Variant chr7-44104848-GCC-G is described in ClinVar as [Pathogenic]. Clinvar id is 3657551.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AEBP1	NM_001129.5 link	c.185_186delCC	p.Pro62HisfsTer75	frameshift_variant	Exon 1 of 21	ENST00000223357.8	NP_001120.3	Q8IUX7-1
AEBP1	XM_011515162.2 link	c.185_186delCC	p.Pro62HisfsTer75	frameshift_variant	Exon 1 of 20		XP_011513464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AEBP1	ENST00000223357.8 link	c.185_186delCC	p.Pro62HisfsTer75	frameshift_variant	Exon 1 of 21	1	NM_001129.5	ENSP00000223357.3		Q8IUX7-1
AEBP1	ENST00000455443.5 link	c.56_57delCC	p.Pro19fs	frameshift_variant	Exon 1 of 6	5		ENSP00000411277.1		H7C3D7

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Jun 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change creates a premature translational stop signal (p.Pro62Hisfs*75) in the AEBP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AEBP1 are known to be pathogenic (PMID: 29606302). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AEBP1-related conditions. For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing