Variant 14-59607408-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021136.3(RTN1):c.1850A>T(p.Gln617Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000385 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

RTN1
NM_021136.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25

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]

RTN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1233165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN1	NM_021136.3 link	c.1850A>T	p.Gln617Leu	missense_variant	Exon 4 of 9	ENST00000267484.10	NP_066959.1	Q16799-1
RTN1	NM_206852.3 link	c.146A>T	p.Gln49Leu	missense_variant	Exon 2 of 7		NP_996734.1	Q16799-3A8K3B9
RTN1	NM_001363702.1 link	c.101A>T	p.Gln34Leu	missense_variant	Exon 2 of 7		NP_001350631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN1	ENST00000267484.10 link	c.1850A>T	p.Gln617Leu	missense_variant	Exon 4 of 9	1	NM_021136.3	ENSP00000267484.5		Q16799-1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000518

AC:

130

AN:

250786

Hom.:

AF XY:

0.000480

AC XY:

AN XY:

135544

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000929

Gnomad NFE exome

AF:

0.000917

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000393

AC:

574

AN:

1461702

Hom.:

Cov.:

AF XY:

0.000371

AC XY:

270

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000637

Gnomad4 NFE exome

AF:

0.000461

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000309

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000428

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000749

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1850A>T (p.Q617L) alteration is located in exon 4 (coding exon 4) of the RTN1 gene. This alteration results from a A to T substitution at nucleotide position 1850, causing the glutamine (Q) at amino acid position 617 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.031

T;.;T;T

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;.;L;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.9

N;N;N;.

REVEL

Benign

0.18

Sift

Benign

0.66

T;T;T;.

Sift4G

Benign

0.65

T;T;T;T

Polyphen

0.0

B;B;P;.

Vest4

0.76

MVP

0.17

MPC

1.6

ClinPred

0.11

GERP RS

6.0

Varity_R

0.32

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over