11-63719394-A-T

Variant names:

• chr11-63719394-A-T
• rs1247048618
• NM_001265589.2:c.892A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001265589.2(RTN3):​c.892A>T​(p.Arg298*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RTN3 NM_001265589.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 0 publications found

Genes affected

RTN3 (HGNC:10469): (reticulon 3) This gene belongs to the reticulon family of highly conserved genes that are preferentially expressed in neuroendocrine tissues. This family of proteins interact with, and modulate the activity of beta-amyloid converting enzyme 1 (BACE1), and the production of amyloid-beta. An increase in the expression of any reticulon protein substantially reduces the production of amyloid-beta, suggesting that reticulon proteins are negative modulators of BACE1 in cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, and pseudogenes of this gene are located on chromosomes 4 and 12. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001265589.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN3	NM_001265589.2	MANE Select	c.892A>T	p.Arg298*	stop_gained	Exon 3 of 9	NP_001252518.1	O95197-1
	RTN3	NM_201428.3		c.835A>T	p.Arg279*	stop_gained	Exon 2 of 8	NP_958831.1	O95197-2
	RTN3	NM_001265590.2		c.556A>T	p.Arg186*	stop_gained	Exon 2 of 8	NP_001252519.1	O95197-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN3	ENST00000377819.10	TSL:1 MANE Select	c.892A>T	p.Arg298*	stop_gained	Exon 3 of 9	ENSP00000367050.5	O95197-1
	RTN3	ENST00000339997.8	TSL:1	c.835A>T	p.Arg279*	stop_gained	Exon 2 of 8	ENSP00000344106.4	O95197-2
	RTN3	ENST00000540798.5	TSL:1	c.556A>T	p.Arg186*	stop_gained	Exon 2 of 8	ENSP00000442733.1	O95197-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	33
DANN	Uncertain	1.0
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.63	D
PhyloP100		0.38
Vest4		0.95
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=26/174	disease causing (fs/PTC)

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: rs1247048618; hg19: chr11-63486866;