16-56369318-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001144.6(AMFR):c.1390A>T(p.Ile464Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AMFR NM_001144.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.27

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
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMFR	NM_001144.6	c.1390A>T	p.Ile464Phe	missense_variant	11/14	ENST00000290649.10
AMFR	NM_001323512.2	c.1486A>T	p.Ile496Phe	missense_variant	12/15
AMFR	NM_001323511.2	c.1105A>T	p.Ile369Phe	missense_variant	11/14
AMFR	XM_005255890.5	c.1105A>T	p.Ile369Phe	missense_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMFR	ENST00000290649.10	c.1390A>T	p.Ile464Phe	missense_variant	11/14	1	NM_001144.6	P1
AMFR	ENST00000492830.5	c.358A>T	p.Ile120Phe	missense_variant	4/7	2
AMFR	ENST00000567738.1	c.631A>T	p.Ile211Phe	missense_variant	6/8	5
AMFR	ENST00000566334.1	n.64A>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.1390A>T (p.I464F) alteration is located in exon 11 (coding exon 11) of the AMFR gene. This alteration results from a A to T substitution at nucleotide position 1390, causing the isoleucine (I) at amino acid position 464 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
Cadd	Pathogenic	29
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;T;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.6	D;.;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D;.;D
Sift4G	Uncertain	0.0040	D;D;.
Polyphen		0.96	D;.;.
Vest4		0.83
MutPred		0.58		Gain of helix (P = 0.132);.;.;
MVP		0.66
MPC		1.7
ClinPred		0.97	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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: chr16-56403230;