chr16-56403084-A-AGGCT

Position:

• chr16-56403084-A-AGGCT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001144.6(AMFR):​c.871_874dupAGCC​(p.Leu292fs) 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 (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AMFR NM_001144.6 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.642

Genes affected

AMFR (HGNC:463): (autocrine motility factor receptor) This locus encodes a glycosylated transmembrane receptor. Its ligand, autocrine motility factor, is a tumor motility-stimulating protein secreted by tumor cells. The encoded receptor is also a member of the E3 ubiquitin ligase family of proteins. It catalyzes ubiquitination and endoplasmic reticulum-associated degradation of specific proteins. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-56403084-A-AGGCT is Pathogenic according to our data. Variant chr16-56403084-A-AGGCT is described in ClinVar as [Pathogenic]. Clinvar id is 2502911.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMFR	NM_001144.6	c.871_874dupAGCC	p.Leu292fs	frameshift_variant	7/14	ENST00000290649.10	NP_001135.3
AMFR	NM_001323512.2	c.871_874dupAGCC	p.Leu292fs	frameshift_variant	7/15		NP_001310441.1
AMFR	NM_001323511.2	c.586_589dupAGCC	p.Leu197fs	frameshift_variant	7/14		NP_001310440.1
AMFR	XM_005255890.5	c.586_589dupAGCC	p.Leu197fs	frameshift_variant	7/14		XP_005255947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMFR	ENST00000290649.10	c.871_874dupAGCC	p.Leu292fs	frameshift_variant	7/14	1	NM_001144.6	ENSP00000290649.5
AMFR	ENST00000492830.5	c.30_33dupAGCC	p.Trp12fs	frameshift_variant	1/7	2		ENSP00000473636.1
AMFR	ENST00000567738.1	c.16_19dupAGCC	p.Leu7fs	frameshift_variant	1/8	5		ENSP00000456288.1
AMFR	ENST00000565445.5	c.586_589dupAGCC	p.Leu197fs	frameshift_variant	7/7	5		ENSP00000456745.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spastic paraplegia 89, autosomal recessive Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-56436996;