chr6-106619221-T-C

Position:

• chr6-106619221-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032730.5(RTN4IP1):​c.601A>G​(p.Lys201Glu) 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. 14/21 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)
• Consequence: RTN4IP1 NM_032730.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39

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]

ACMG classification

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=0.096200645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN4IP1	NM_032730.5	c.601A>G	p.Lys201Glu	missense_variant	4/9	ENST00000369063.8	NP_116119.2
RTN4IP1	NM_001318746.1	c.301A>G	p.Lys101Glu	missense_variant	4/9		NP_001305675.1
RTN4IP1	XM_011536192.3	c.361A>G	p.Lys121Glu	missense_variant	5/10		XP_011534494.1
RTN4IP1	XM_017011376.3	c.601A>G	p.Lys201Glu	missense_variant	4/8		XP_016866865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN4IP1	ENST00000369063.8	c.601A>G	p.Lys201Glu	missense_variant	4/9	1	NM_032730.5	ENSP00000358059.3
RTN4IP1	ENST00000539449.2	c.601A>G	p.Lys201Glu	missense_variant	4/6	2		ENSP00000444261.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.17	N;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.084
Sift	Benign	0.44	T;T
Sift4G	Benign	0.78	T;T
Polyphen		0.0	B;B
Vest4		0.13
MutPred		0.47		Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);
MVP		0.33
MPC		0.21
ClinPred		0.31	T
GERP RS		5.0
Varity_R		0.36
gMVP		0.49

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

Other links and lift over

dbSNP: rs200457692; hg19: chr6-107067096;