rs752724559

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021136.3(RTN1):​c.2278G>T​(p.Val760Phe) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Consequence

RTN1
NM_021136.3 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.65
Variant links:
Genes affected
RTN1 (HGNC:10467): (reticulon 1) This gene belongs to the family of reticulon encoding genes. Reticulons are associated with the endoplasmic reticulum, and are involved in neuroendocrine secretion or in membrane trafficking in neuroendocrine cells. This gene is considered to be a specific marker for neurological diseases and cancer, and is a potential molecular target for therapy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41122502).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RTN1NM_021136.3 linkc.2278G>T p.Val760Phe missense_variant Exon 8 of 9 ENST00000267484.10 NP_066959.1 Q16799-1
RTN1NM_206852.3 linkc.574G>T p.Val192Phe missense_variant Exon 6 of 7 NP_996734.1 Q16799-3A8K3B9
RTN1NM_001363702.1 linkc.529G>T p.Val177Phe missense_variant Exon 6 of 7 NP_001350631.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RTN1ENST00000267484.10 linkc.2278G>T p.Val760Phe missense_variant Exon 8 of 9 1 NM_021136.3 ENSP00000267484.5 Q16799-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Uncertain
0.028
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.075
T;.;T;T
Eigen
Benign
0.013
Eigen_PC
Benign
-0.0064
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Benign
0.063
D
MetaRNN
Benign
0.41
T;T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
1.9
.;.;L;.
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-3.1
D;D;D;.
REVEL
Benign
0.26
Sift
Benign
0.060
T;T;D;.
Sift4G
Benign
0.40
T;T;D;D
Polyphen
0.60
P;P;D;.
Vest4
0.52
MutPred
0.52
.;.;Gain of catalytic residue at V760 (P = 0.0432);.;
MVP
0.25
MPC
1.9
ClinPred
0.98
D
GERP RS
1.2
Varity_R
0.31
gMVP
0.99

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs752724559; hg19: chr14-60069793; API