16-56362574-C-T

Variant names:

• chr16-56362574-C-T
• rs4924
• NM_001144.6:c.*335G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001323512.2(AMFR):​c.*335G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 585,466 control chromosomes in the GnomAD database, including 92,818 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 0.59 (27404 hom., cov: 32)
  • Exomes 𝑓: 0.54 (65414 hom.)
• Consequence: AMFR NM_001323512.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 43 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (REVEL=0.004).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323512.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMFR	NM_001144.6	MANE Select	c.*335G>A		3_prime_UTR	Exon 14 of 14	NP_001135.3
	AMFR	NM_001323512.2		c.*335G>A		3_prime_UTR	Exon 15 of 15	NP_001310441.1
	AMFR	NM_001323511.2		c.*335G>A		3_prime_UTR	Exon 14 of 14	NP_001310440.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMFR	ENST00000290649.10	TSL:1 MANE Select	c.*335G>A		3_prime_UTR	Exon 14 of 14	ENSP00000290649.5
	AMFR	ENST00000861442.1		c.*335G>A		3_prime_UTR	Exon 14 of 14	ENSP00000531501.1
	AMFR	ENST00000861443.1		c.*335G>A		3_prime_UTR	Exon 14 of 14	ENSP00000531502.1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89100 AN: 151844 Hom.: 27378 Cov.: 32

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.563

GnomAD2 exomes AF: 0.545 AC: 126233 AN: 231608 AF XY: 0.544

Gnomad AFR exome AF: 0.772

Gnomad AMR exome AF: 0.567

Gnomad ASJ exome AF: 0.537

Gnomad EAS exome AF: 0.418

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.528

Gnomad OTH exome AF: 0.528

GnomAD4 exome AF: 0.543 AC: 235598 AN: 433504 Hom.: 65414 Cov.: 2 AF XY: 0.547 AC XY: 133340 AN XY: 243590

African (AFR) AF: 0.764 AC: 10060 AN: 13160

American (AMR) AF: 0.567 AC: 21670 AN: 38234

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 7806 AN: 14674

East Asian (EAS) AF: 0.465 AC: 8838 AN: 18994

South Asian (SAS) AF: 0.611 AC: 41158 AN: 67376

European-Finnish (FIN) AF: 0.404 AC: 8463 AN: 20928

Middle Eastern (MID) AF: 0.550 AC: 1778 AN: 3234

European-Non Finnish (NFE) AF: 0.528 AC: 124392 AN: 235408

Other (OTH) AF: 0.532 AC: 11433 AN: 21496

GnomAD4 genome AF: 0.587 AC: 89168 AN: 151962 Hom.: 27404 Cov.: 32 AF XY: 0.580 AC XY: 43065 AN XY: 74270

African (AFR) AF: 0.762 AC: 31582 AN: 41470

American (AMR) AF: 0.548 AC: 8386 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1838 AN: 3466

East Asian (EAS) AF: 0.436 AC: 2246 AN: 5150

South Asian (SAS) AF: 0.605 AC: 2917 AN: 4818

European-Finnish (FIN) AF: 0.392 AC: 4138 AN: 10566

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36214 AN: 67886

Other (OTH) AF: 0.559 AC: 1180 AN: 2110

Alfa AF: 0.553 Hom.: 99847

Bravo AF: 0.605

Asia WGS AF: 0.547 AC: 1904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.50
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4924; hg19: chr16-56396486; COSMIC: COSV51923832; COSMIC: COSV51923832;