16-56369323-T-C

Variant names:

• chr16-56369323-T-C
• rs762380239
• NM_001144.6:c.1385A>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.1385A>G​(p.His462Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: AMFR NM_001144.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.27

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=0.17237532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMFR	NM_001144.6	c.1385A>G	p.His462Arg	missense_variant	Exon 11 of 14	ENST00000290649.10	NP_001135.3
AMFR	NM_001323512.2	c.1481A>G	p.His494Arg	missense_variant	Exon 12 of 15		NP_001310441.1
AMFR	NM_001323511.2	c.1100A>G	p.His367Arg	missense_variant	Exon 11 of 14		NP_001310440.1
AMFR	XM_005255890.5	c.1100A>G	p.His367Arg	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.1385A>G	p.His462Arg	missense_variant	Exon 11 of 14	1	NM_001144.6	ENSP00000290649.5
AMFR	ENST00000492830.5	c.353A>G	p.His118Arg	missense_variant	Exon 4 of 7	2		ENSP00000473636.1
AMFR	ENST00000567738.1	c.626A>G	p.His209Arg	missense_variant	Exon 6 of 8	5		ENSP00000456288.1
AMFR	ENST00000566334.1	n.59A>G		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461562 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727066

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152238 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74376

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.14	T;T;.
Eigen	Benign	-0.25
Eigen_PC	Benign	0.035
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T;T;D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	N;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.97	N;.;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;.;T
Sift4G	Benign	1.0	T;T;.
Polyphen		0.0010	B;.;.
Vest4		0.49
MutPred		0.48		Gain of helix (P = 0.0696);.;.;
MVP		0.36
MPC		0.62
ClinPred		0.49	T
GERP RS		6.0
Varity_R		0.31
gMVP		0.76

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: rs762380239; hg19: chr16-56403235;