Genetic Variant NM_001144.6:c.1817C>A (chr16-56363024-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001144.6(AMFR):c.1817C>A(p.Ala606Glu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A606V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

AMFR
NM_001144.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.715

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

spastic paraplegia 89, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P

AMFR links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014288008).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AMFR	NM_001144.6	MANE Select	c.1817C>A	p.Ala606Glu	missense	Exon 14 of 14	NP_001135.3
AMFR	NM_001323512.2		c.1913C>A	p.Ala638Glu	missense	Exon 15 of 15	NP_001310441.1
AMFR	NM_001323511.2		c.1532C>A	p.Ala511Glu	missense	Exon 14 of 14	NP_001310440.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMFR	ENST00000290649.10	TSL:1 MANE Select	c.1817C>A	p.Ala606Glu	missense	Exon 14 of 14	ENSP00000290649.5	Q9UKV5
AMFR	ENST00000861442.1		c.1799C>A	p.Ala600Glu	missense	Exon 14 of 14	ENSP00000531501.1
AMFR	ENST00000861443.1		c.1787C>A	p.Ala596Glu	missense	Exon 14 of 14	ENSP00000531502.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249362

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.1

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.10

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.48

M_CAP

Benign

0.0064

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

PhyloP100

0.71

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.15

REVEL

Benign

0.074

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.13

MutPred

0.069

Gain of solvent accessibility (P = 0.1185)

MVP

0.10

MPC

0.59

ClinPred

0.016

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.030

gMVP

0.091

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over