rs542998

Variant names:

• chr11-63719914-T-A
• rs542998
• NM_001265589.2:c.1412T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-63719914-T-A
• chr11-63719914-T-C
• chr11-63719914-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001265589.2(RTN3):​c.1412T>A​(p.Val471Asp) 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. 15/22 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. V471F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RTN3 NM_001265589.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 47 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.122528315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN3	NM_001265589.2	c.1412T>A	p.Val471Asp	missense_variant	Exon 3 of 9	ENST00000377819.10	NP_001252518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN3	ENST00000377819.10	c.1412T>A	p.Val471Asp	missense_variant	Exon 3 of 9	1	NM_001265589.2	ENSP00000367050.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 163974

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.9
DANN	Benign	0.92
DEOGEN2	Benign	0.046	T;.;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.;.
PhyloP100		-0.073
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.2	N;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.064	T;D;T
Polyphen		0.93	P;D;.
Vest4		0.30
MutPred		0.17		Loss of methylation at K469 (P = 0.0438);.;.;
MVP		0.13
MPC		0.094
ClinPred		0.62	D
GERP RS		-2.9
Varity_R		0.35
gMVP		0.076
Mutation Taster		=97/3	polymorphism

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: rs542998; hg19: chr11-63487386;