Variant 6-106572096-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032730.5(RTN4IP1):c.1091C>G(p.Pro364Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RTN4IP1
NM_032730.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89

Variant links:

Genes affected

RTN4IP1 (HGNC:18647): (reticulon 4 interacting protein 1) This gene encodes a mitochondrial protein that interacts with reticulon 4, which is a potent inhibitor of regeneration following spinal cord injury. This interaction may be important for reticulon-induced inhibition of neurite growth. Mutations in this gene can cause optic atrophy 10, with or without ataxia, cognitive disability, and seizures. There is a pseudogene for this gene on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

RTN4IP1 links:

RTN4IP1 (HGNC:):

RTN4IP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN4IP1	NM_032730.5 linkuse as main transcript	c.1091C>G	p.Pro364Arg	missense_variant	9/9	ENST00000369063.8	NP_116119.2	Q8WWV3-1
RTN4IP1	NM_001318746.1 linkuse as main transcript	c.791C>G	p.Pro264Arg	missense_variant	9/9		NP_001305675.1	Q8WWV3-2
RTN4IP1	XM_011536192.3 linkuse as main transcript	c.851C>G	p.Pro284Arg	missense_variant	10/10		XP_011534494.1
RTN4IP1	XM_017011376.3 linkuse as main transcript	c.*40C>G		3_prime_UTR_variant	8/8		XP_016866865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RTN4IP1	ENST00000369063.8 linkuse as main transcript	c.1091C>G	p.Pro364Arg	missense_variant	9/9	1	NM_032730.5	ENSP00000358059.3	Q8WWV3-1
RTN4IP1	ENST00000539449 linkuse as main transcript	c.*40C>G		3_prime_UTR_variant	6/6	2		ENSP00000444261.1	G3V1R2
RTN4IP1	ENST00000493619.1 linkuse as main transcript	n.89C>G		non_coding_transcript_exon_variant	2/2	3
RTN4IP1	ENST00000498091.1 linkuse as main transcript	n.312C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250510

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135510

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726780

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 02, 2024

The c.1091C>G (p.P364R) alteration is located in exon 9 (coding exon 9) of the RTN4IP1 gene. This alteration results from a C to G substitution at nucleotide position 1091, causing the proline (P) at amino acid position 364 to be replaced by an arginine (R). 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

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.98

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.081

MetaRNN

Pathogenic

0.90

MetaSVM

Benign

-0.29

MutationAssessor

Pathogenic

4.3

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-7.5

REVEL

Uncertain

0.57

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.90

MutPred

0.66

Loss of sheet (P = 0.007);

MVP

0.74

MPC

0.65

ClinPred

1.0

GERP RS

6.0

Varity_R

0.75

gMVP

0.86

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

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