NM_001144.6:c.1166G>C

Variant names:

• chr16-56389295-C-G
• rs758196891
• NM_001144.6:c.1166G>C

Variant summary

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

The NM_001144.6(AMFR):​c.1166G>C​(p.Arg389Pro) variant causes a missense 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. 14/21 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: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13785857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMFR	NM_001144.6	c.1166G>C	p.Arg389Pro	missense_variant	Exon 9 of 14	ENST00000290649.10	NP_001135.3
AMFR	NM_001323512.2	c.1166G>C	p.Arg389Pro	missense_variant	Exon 9 of 15		NP_001310441.1
AMFR	NM_001323511.2	c.881G>C	p.Arg294Pro	missense_variant	Exon 9 of 14		NP_001310440.1
AMFR	XM_005255890.5	c.881G>C	p.Arg294Pro	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.1166G>C	p.Arg389Pro	missense_variant	Exon 9 of 14	1	NM_001144.6	ENSP00000290649.5
AMFR	ENST00000567738.1	c.311G>C	p.Arg104Pro	missense_variant	Exon 3 of 8	5		ENSP00000456288.1
AMFR	ENST00000492830.5	c.245-3273G>C		intron_variant	Intron 2 of 6	2		ENSP00000473636.1
AMFR	ENST00000568762.1	n.44-3273G>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.074
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.057
Sift	Benign	0.14	T;T
Sift4G	Benign	0.15	T;.
Polyphen		0.0010	B;.
Vest4		0.22
MutPred		0.36		Loss of stability (P = 0.0977);.;
MVP		0.49
MPC		0.74
ClinPred		0.57	D
GERP RS		5.9
Varity_R		0.20
gMVP		0.55

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

LitVar

Other links and lift over

dbSNP: rs758196891; hg19: chr16-56423207;