16-56367527-G-T

Variant names:

• chr16-56367527-G-T
• rs202074356
• NM_001144.6:c.1516C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144.6(AMFR):​c.1516C>A​(p.Arg506Arg) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000137 in 1,460,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AMFR NM_001144.6 splice_region, synonymous
• Scores: Splicing: ADA: 0.006390
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.74

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]

ACMG classification

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 (BayesDel_noAF=-0.4).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMFR	NM_001144.6	c.1516C>A	p.Arg506Arg	splice_region_variant, synonymous_variant	Exon 12 of 14	ENST00000290649.10	NP_001135.3
AMFR	NM_001323512.2	c.1612C>A	p.Arg538Arg	splice_region_variant, synonymous_variant	Exon 13 of 15		NP_001310441.1
AMFR	NM_001323511.2	c.1231C>A	p.Arg411Arg	splice_region_variant, synonymous_variant	Exon 12 of 14		NP_001310440.1
AMFR	XM_005255890.5	c.1231C>A	p.Arg411Arg	splice_region_variant, synonymous_variant	Exon 12 of 14		XP_005255947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMFR	ENST00000290649.10	c.1516C>A	p.Arg506Arg	splice_region_variant, synonymous_variant	Exon 12 of 14	1	NM_001144.6	ENSP00000290649.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460770 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726740

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0064
dbscSNV1_RF	Benign	0.030
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs202074356; hg19: chr16-56401439;