16-56389323-T-G

Position:

• chr16-56389323-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144.6(AMFR):​c.1138A>C​(p.Met380Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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)
• Consequence: AMFR NM_001144.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.99

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26298434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMFR	NM_001144.6	c.1138A>C	p.Met380Leu	missense_variant	9/14	ENST00000290649.10	NP_001135.3
AMFR	NM_001323512.2	c.1138A>C	p.Met380Leu	missense_variant	9/15		NP_001310441.1
AMFR	NM_001323511.2	c.853A>C	p.Met285Leu	missense_variant	9/14		NP_001310440.1
AMFR	XM_005255890.5	c.853A>C	p.Met285Leu	missense_variant	9/14		XP_005255947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMFR	ENST00000290649.10	c.1138A>C	p.Met380Leu	missense_variant	9/14	1	NM_001144.6	ENSP00000290649.5
AMFR	ENST00000567738.1	c.283A>C	p.Met95Leu	missense_variant	3/8	5		ENSP00000456288.1
AMFR	ENST00000492830.5	c.245-3301A>C		intron_variant		2		ENSP00000473636.1
AMFR	ENST00000568762.1	n.44-3301A>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 24, 2024

The c.1138A>C (p.M380L) alteration is located in exon 9 (coding exon 9) of the AMFR gene. This alteration results from a A to C substitution at nucleotide position 1138, causing the methionine (M) at amino acid position 380 to be replaced by a leucine (L). 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	Benign	0.19
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.097	T;.
Eigen	Benign	-0.094
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.88	L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.43	N;N
REVEL	Benign	0.20
Sift	Benign	0.73	T;T
Sift4G	Benign	1.0	T;.
Polyphen		0.0030	B;.
Vest4		0.45
MutPred		0.47		Loss of catalytic residue at M380 (P = 0.0746);.;
MVP		0.52
MPC		0.48
ClinPred		0.67	D
GERP RS		5.9
Varity_R		0.33
gMVP		0.46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-56423235;