16-56389364-C-G

Variant names:

• chr16-56389364-C-G
• rs745966114
• NM_001144.6:c.1097G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001144.6(AMFR):​c.1097G>C​(p.Arg366Pro) 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 pathogenic 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: Not reported in ClinVar
• Conservation: PhyloP100: 7.88

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMFR	NM_001144.6	c.1097G>C	p.Arg366Pro	missense_variant	Exon 9 of 14	ENST00000290649.10	NP_001135.3
AMFR	NM_001323512.2	c.1097G>C	p.Arg366Pro	missense_variant	Exon 9 of 15		NP_001310441.1
AMFR	NM_001323511.2	c.812G>C	p.Arg271Pro	missense_variant	Exon 9 of 14		NP_001310440.1
AMFR	XM_005255890.5	c.812G>C	p.Arg271Pro	missense_variant	Exon 9 of 14		XP_005255947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMFR	ENST00000290649.10	c.1097G>C	p.Arg366Pro	missense_variant	Exon 9 of 14	1	NM_001144.6	ENSP00000290649.5
AMFR	ENST00000567738.1	c.242G>C	p.Arg81Pro	missense_variant	Exon 3 of 8	5		ENSP00000456288.1
AMFR	ENST00000492830.5	c.245-3342G>C		intron_variant	Intron 2 of 6	2		ENSP00000473636.1
AMFR	ENST00000568762.1	n.44-3342G>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Pathogenic	3.6	H;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.033	D;.
Polyphen		0.97	D;.
Vest4		0.93
MutPred		0.79		Loss of catalytic residue at R366 (P = 0.0432);.;
MVP		0.67
MPC		1.6
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.79
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs745966114; hg19: chr16-56423276; COSMIC: COSV51921033; COSMIC: COSV51921033;