Variant 16-56369318-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000290649.10(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
ENST00000290649.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.27

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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	Protein
AMFR	NM_001144.6 linkuse as main transcript	c.1390A>T	p.Ile464Phe	missense_variant	11/14	ENST00000290649.10	NP_001135.3
AMFR	NM_001323512.2 linkuse as main transcript	c.1486A>T	p.Ile496Phe	missense_variant	12/15		NP_001310441.1
AMFR	NM_001323511.2 linkuse as main transcript	c.1105A>T	p.Ile369Phe	missense_variant	11/14		NP_001310440.1
AMFR	XM_005255890.5 linkuse as main transcript	c.1105A>T	p.Ile369Phe	missense_variant	11/14		XP_005255947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
AMFR	ENST00000290649.10 linkuse as main transcript	c.1390A>T	p.Ile464Phe	missense_variant	11/14	1	NM_001144.6	ENSP00000290649	P1
AMFR	ENST00000492830.5 linkuse as main transcript	c.358A>T	p.Ile120Phe	missense_variant	4/7	2		ENSP00000473636
AMFR	ENST00000567738.1 linkuse as main transcript	c.631A>T	p.Ile211Phe	missense_variant	6/8	5		ENSP00000456288
AMFR	ENST00000566334.1 linkuse as main transcript	n.64A>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

T;T;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.75

D;D;D

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.90

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over