19-45494700-T-G

Variant summary

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

The NM_005619.5(RTN2):​c.385A>C​(p.Thr129Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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‘“: 6.8e-7 ( 0 hom. )

Consequence

RTN2
NM_005619.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.11
Variant links:
Genes affected
RTN2 (HGNC:10468): (reticulon 2) 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. Reticulon proteins also play an important role in the replication of positive-strand RNA (ssRNA) viruses. Mutations at this locus have been associated with autosomal dominant spastic paraplegia-12. [provided by RefSeq, Aug 2020]
PPM1N (HGNC:26845): (protein phosphatase, Mg2+/Mn2+ dependent 1N (putative)) Predicted to enable metal ion binding activity and protein serine/threonine phosphatase activity. Predicted to be involved in negative regulation of I-kappaB kinase/NF-kappaB signaling and positive regulation of canonical Wnt signaling pathway. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.030166686).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RTN2NM_005619.5 linkc.385A>C p.Thr129Pro missense_variant Exon 3 of 11 ENST00000245923.9 NP_005610.1 O75298-1A8K7F2Q6GMT0
RTN2NM_206900.3 linkc.385A>C p.Thr129Pro missense_variant Exon 3 of 10 NP_996783.1 O75298-2A8K7F2Q6GMT0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RTN2ENST00000245923.9 linkc.385A>C p.Thr129Pro missense_variant Exon 3 of 11 1 NM_005619.5 ENSP00000245923.3 O75298-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461208
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726936
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:
8.99e-7
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
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.083
DANN
Benign
0.68
DEOGEN2
Benign
0.092
T;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0060
N
LIST_S2
Benign
0.47
T;T
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.030
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N;N
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.022
Sift
Benign
0.14
T;T
Sift4G
Benign
0.34
T;T
Polyphen
0.0
B;B
Vest4
0.089
MutPred
0.17
Loss of phosphorylation at T129 (P = 0.0053);Loss of phosphorylation at T129 (P = 0.0053);
MVP
0.068
MPC
0.36
ClinPred
0.078
T
GERP RS
-7.7
Varity_R
0.16
gMVP
0.16

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-45997958; API