Variant 16-56369323-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.27

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 link	c.1385A>G	p.His462Arg	missense_variant	Exon 11 of 14	ENST00000290649.10	NP_001135.3	Q9UKV5
AMFR	NM_001323512.2 link	c.1481A>G	p.His494Arg	missense_variant	Exon 12 of 15		NP_001310441.1	Q9UKV5
AMFR	NM_001323511.2 link	c.1100A>G	p.His367Arg	missense_variant	Exon 11 of 14		NP_001310440.1	A0A024R6R5
AMFR	XM_005255890.5 link	c.1100A>G	p.His367Arg	missense_variant	Exon 11 of 14		XP_005255947.1	A0A024R6R5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AMFR	ENST00000290649.10 link	c.1385A>G	p.His462Arg	missense_variant	Exon 11 of 14	1	NM_001144.6	ENSP00000290649.5	Q9UKV5
AMFR	ENST00000492830.5 link	c.353A>G	p.His118Arg	missense_variant	Exon 4 of 7	2		ENSP00000473636.1	R4GNG2
AMFR	ENST00000567738.1 link	c.626A>G	p.His209Arg	missense_variant	Exon 6 of 8	5		ENSP00000456288.1	H3BRK9
AMFR	ENST00000566334.1 link	n.59A>G		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

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:

AN:

1461562

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727066

show subpopulations

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:

AN:

152238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74376

show subpopulations

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

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.14

T;T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

0.035

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

T;T;D

M_CAP

Benign

0.0077

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.46

N;.;.

PrimateAI

Pathogenic

0.86

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over