Genetic Variant NM_001144.6:c.*1211C>T (chr16-56361698-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001144.6(AMFR):c.*1211C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 147,420 control chromosomes in the GnomAD database, including 33,375 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.66 ( 33338 hom., cov: 24)

Exomes 𝑓: 0.45 ( 37 hom. )

Consequence

AMFR
NM_001144.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.67

Publications

19 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: G2P, Labcorp Genetics (formerly Invitae)

AMFR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
AMFR	NM_001144.6 link	c.*1211C>T	3_prime_UTR_variant	Exon 14 of 14	ENST00000290649.10	NP_001135.3
AMFR	NM_001323512.2 link	c.*1211C>T	3_prime_UTR_variant	Exon 15 of 15		NP_001310441.1
AMFR	NM_001323511.2 link	c.*1211C>T	3_prime_UTR_variant	Exon 14 of 14		NP_001310440.1
AMFR	XM_005255890.5 link	c.*1211C>T	3_prime_UTR_variant	Exon 14 of 14		XP_005255947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMFR	ENST00000290649.10 link	c.*1211C>T		3_prime_UTR_variant	Exon 14 of 14	1	NM_001144.6	ENSP00000290649.5
AMFR	ENST00000492830.5 link	c.*1211C>T		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000473636.1

Frequencies

GnomAD3 genomes

AF:

0.661

AC:

97050

AN:

146900

Hom.:

33297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.868

Gnomad AMI

AF:

0.594

Gnomad AMR

AF:

0.609

Gnomad ASJ

AF:

0.553

Gnomad EAS

AF:

0.607

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.526

Gnomad NFE

AF:

0.578

Gnomad OTH

AF:

0.634

GnomAD4 exome

AF:

0.451

AC:

194

AN:

430

Hom.:

Cov.:

AF XY:

0.465

AC XY:

120

AN XY:

258

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.445

AC:

187

AN:

420

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.661

AC:

97131

AN:

146990

Hom.:

33338

Cov.:

AF XY:

0.659

AC XY:

46843

AN XY:

71042

show subpopulations

African (AFR)

AF:

0.868

AC:

35089

AN:

40418

American (AMR)

AF:

0.609

AC:

8884

AN:

14590

Ashkenazi Jewish (ASJ)

AF:

0.553

AC:

1906

AN:

3448

East Asian (EAS)

AF:

0.607

AC:

2997

AN:

4938

South Asian (SAS)

AF:

0.729

AC:

3399

AN:

4664

European-Finnish (FIN)

AF:

0.479

AC:

4138

AN:

8642

Middle Eastern (MID)

AF:

0.532

AC:

149

AN:

280

European-Non Finnish (NFE)

AF:

0.578

AC:

38769

AN:

67116

Other (OTH)

AF:

0.634

AC:

1270

AN:

2002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

1443

2886

4328

5771

7214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.602

Hom.:

15633

Bravo

AF:

0.671

Asia WGS

AF:

0.707

AC:

2454

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.1

(source)

DANN

Benign

0.52

PhyloP100

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over