chr16-56362574-C-G

Variant names:

• chr16-56362574-C-G
• rs4924
• NM_001144.6:c.*335G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001323512.2(AMFR):​c.*335G>C 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AMFR NM_001323512.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 43 publications found

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]

AMFR Gene-Disease associations (from GenCC):

• spastic paraplegia 89, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.103).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323512.2. 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
	AMFR	NM_001144.6	MANE Select	c.*335G>C		3_prime_UTR	Exon 14 of 14	NP_001135.3
	AMFR	NM_001323512.2		c.*335G>C		3_prime_UTR	Exon 15 of 15	NP_001310441.1
	AMFR	NM_001323511.2		c.*335G>C		3_prime_UTR	Exon 14 of 14	NP_001310440.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMFR	ENST00000290649.10	TSL:1 MANE Select	c.*335G>C		3_prime_UTR	Exon 14 of 14	ENSP00000290649.5
	AMFR	ENST00000861442.1		c.*335G>C		3_prime_UTR	Exon 14 of 14	ENSP00000531501.1
	AMFR	ENST00000861443.1		c.*335G>C		3_prime_UTR	Exon 14 of 14	ENSP00000531502.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 433798 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 243722

African (AFR) AF: 0.00 AC: 0 AN: 13170

American (AMR) AF: 0.00 AC: 0 AN: 38242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14678

East Asian (EAS) AF: 0.00 AC: 0 AN: 19014

South Asian (SAS) AF: 0.00 AC: 0 AN: 67378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3234

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 235612

Other (OTH) AF: 0.00 AC: 0 AN: 21518

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.16
DANN	Benign	0.46
PhyloP100		-0.34

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: rs4924; hg19: chr16-56396486;