chr2-54973570-T-A

Variant names:

• chr2-54973570-T-A
• rs752685497
• NM_020532.5:c.3529A>T

Variant summary

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

The NM_020532.5(RTN4):​c.3529A>T​(p.Met1177Leu) 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. 15/21 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: RTN4 NM_020532.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427

Genes affected

RTN4 (HGNC:14085): (reticulon 4) 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. The product of this gene is a potent neurite outgrowth inhibitor which may also help block the regeneration of the central nervous system in higher vertebrates. Alternatively spliced transcript variants derived both from differential splicing and differential promoter usage and encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

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=0.1205191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN4	NM_020532.5	c.3529A>T	p.Met1177Leu	missense_variant	Exon 8 of 9	ENST00000337526.11	NP_065393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN4	ENST00000337526.11	c.3529A>T	p.Met1177Leu	missense_variant	Exon 8 of 9	1	NM_020532.5	ENSP00000337838.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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	0.18
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.84
DEOGEN2	Benign	0.13	.;.;.;T;.;.;.;.;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.82	T;.;.;T;T;T;.;T;T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;.;.;L;.;.;.;.;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N;N;N;N;N;N;N;N;.;N
REVEL	Benign	0.20
Sift	Benign	0.36	T;T;T;T;T;T;T;T;.;T
Sift4G	Benign	0.63	T;T;T;T;T;T;T;T;T;.
Polyphen		0.88, 0.11	.;.;.;P;.;B;.;.;.;.
Vest4		0.40
MutPred		0.49		.;.;.;Loss of catalytic residue at V1173 (P = 0.0599);.;.;.;.;.;.;
MVP		0.22
MPC		0.028
ClinPred		0.47	T
GERP RS		2.4
Varity_R		0.14
gMVP		0.35

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

Other links and lift over

dbSNP: rs752685497; hg19: chr2-55200706;