rs750744117

Variant names:

• chr16-56369218-C-G
• rs750744117
• NM_001144.6:c.1490G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-56369218-C-G
• chr16-56369218-C-T

Variant summary

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

The NM_001144.6(AMFR):​c.1490G>C​(p.Arg497Pro) 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: 33)
• Consequence: AMFR NM_001144.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.89

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMFR	NM_001144.6	c.1490G>C	p.Arg497Pro	missense_variant	Exon 11 of 14	ENST00000290649.10	NP_001135.3
AMFR	NM_001323512.2	c.1586G>C	p.Arg529Pro	missense_variant	Exon 12 of 15		NP_001310441.1
AMFR	NM_001323511.2	c.1205G>C	p.Arg402Pro	missense_variant	Exon 11 of 14		NP_001310440.1
AMFR	XM_005255890.5	c.1205G>C	p.Arg402Pro	missense_variant	Exon 11 of 14		XP_005255947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMFR	ENST00000290649.10	c.1490G>C	p.Arg497Pro	missense_variant	Exon 11 of 14	1	NM_001144.6	ENSP00000290649.5
AMFR	ENST00000492830.5	c.458G>C	p.Arg153Pro	missense_variant	Exon 4 of 7	2		ENSP00000473636.1
AMFR	ENST00000567738.1	c.731G>C	p.Arg244Pro	missense_variant	Exon 6 of 8	5		ENSP00000456288.1
AMFR	ENST00000566334.1	n.164G>C		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;T;.
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.063	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.3	D;.;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.021	D;.;D
Sift4G	Uncertain	0.014	D;D;.
Polyphen		1.0	D;.;.
Vest4		0.92
MutPred		0.70		Gain of helix (P = 0.062);.;.;
MVP		0.69
MPC		1.7
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.91
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs750744117; hg19: chr16-56403130;