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

Variant summary

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

The NM_001144.6(AMFR):c.1385A>T(p.His462Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000157 in 1,461,562 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

AMFR
NM_001144.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

AMFR (HGNC:):

AMFR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMFR	NM_001144.6 linkuse as main transcript	c.1385A>T	p.His462Leu	missense_variant	11/14	ENST00000290649.10	NP_001135.3	Q9UKV5
AMFR	NM_001323512.2 linkuse as main transcript	c.1481A>T	p.His494Leu	missense_variant	12/15		NP_001310441.1	Q9UKV5
AMFR	NM_001323511.2 linkuse as main transcript	c.1100A>T	p.His367Leu	missense_variant	11/14		NP_001310440.1	A0A024R6R5
AMFR	XM_005255890.5 linkuse as main transcript	c.1100A>T	p.His367Leu	missense_variant	11/14		XP_005255947.1	A0A024R6R5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AMFR	ENST00000290649.10 linkuse as main transcript	c.1385A>T	p.His462Leu	missense_variant	11/14	1	NM_001144.6	ENSP00000290649.5	Q9UKV5
AMFR	ENST00000492830.5 linkuse as main transcript	c.353A>T	p.His118Leu	missense_variant	4/7	2		ENSP00000473636.1	R4GNG2
AMFR	ENST00000567738.1 linkuse as main transcript	c.626A>T	p.His209Leu	missense_variant	6/8	5		ENSP00000456288.1	H3BRK9
AMFR	ENST00000566334.1 linkuse as main transcript	n.59A>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250988

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461562

Hom.:

Cov.:

AF XY:

0.00000963

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:

0.0000189

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.1385A>T (p.H462L) alteration is located in exon 11 (coding exon 11) of the AMFR gene. This alteration results from a A to T substitution at nucleotide position 1385, causing the histidine (H) at amino acid position 462 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

0.0070

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.30

T;T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-4.8

D;.;D

REVEL

Benign

0.19

Sift

Benign

0.056

T;.;T

Sift4G

Uncertain

0.044

D;D;.

Polyphen

0.24

B;.;.

Vest4

0.79

MVP

0.46

MPC

0.99

ClinPred

0.84

GERP RS

6.0

Varity_R

0.58

gMVP

0.84

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over