rs758276986

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021136.3(RTN1):ā€‹c.916A>Gā€‹(p.Ile306Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

RTN1
NM_021136.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04144475).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RTN1NM_021136.3 linkc.916A>G p.Ile306Val missense_variant Exon 2 of 9 ENST00000267484.10 NP_066959.1 Q16799-1
RTN1XM_011537063.4 linkc.916A>G p.Ile306Val missense_variant Exon 2 of 4 XP_011535365.1
RTN1XM_047431674.1 linkc.916A>G p.Ile306Val missense_variant Exon 2 of 4 XP_047287630.1
RTN1XR_007064042.1 linkn.1062A>G non_coding_transcript_exon_variant Exon 2 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RTN1ENST00000267484.10 linkc.916A>G p.Ile306Val missense_variant Exon 2 of 9 1 NM_021136.3 ENSP00000267484.5 Q16799-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461882
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727242
show subpopulations
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.81
CADD
Benign
1.0
DANN
Benign
0.72
DEOGEN2
Benign
0.0042
T;T
Eigen
Benign
-0.99
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.057
N
LIST_S2
Benign
0.50
T;T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.041
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.75
N;.
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.010
N;.
REVEL
Benign
0.014
Sift
Benign
0.52
T;.
Sift4G
Benign
0.82
T;T
Polyphen
0.0
B;.
Vest4
0.082
MutPred
0.22
Gain of glycosylation at S311 (P = 0.1421);.;
MVP
0.043
MPC
0.084
ClinPred
0.030
T
GERP RS
-1.8
Varity_R
0.030
gMVP
0.063

Splicing

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: rs758276986; hg19: chr14-60212525; API