2-54982570-G-A

Variant names:

• chr2-54982570-G-A
• rs142622923
• NM_020532.5:c.3305C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020532.5(RTN4):​c.3305C>T​(p.Thr1102Met) variant causes a missense change. The variant allele was found at a frequency of 0.000062 in 1,613,584 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 0.00015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: RTN4 NM_020532.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16515651).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020532.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN4	NM_020532.5	MANE Select	c.3305C>T	p.Thr1102Met	missense	Exon 5 of 9	NP_065393.1	Q9NQC3-1
	RTN4	NM_001321859.2		c.2687C>T	p.Thr896Met	missense	Exon 5 of 9	NP_001308788.1	Q9NQC3-6
	RTN4	NM_001321860.1		c.2687C>T	p.Thr896Met	missense	Exon 5 of 9	NP_001308789.1	Q9NQC3-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN4	ENST00000337526.11	TSL:1 MANE Select	c.3305C>T	p.Thr1102Met	missense	Exon 5 of 9	ENSP00000337838.6	Q9NQC3-1
	RTN4	ENST00000357376.7	TSL:1	c.2687C>T	p.Thr896Met	missense	Exon 5 of 9	ENSP00000349944.3	Q9NQC3-6
	RTN4	ENST00000394611.6	TSL:1	c.2687C>T	p.Thr896Met	missense	Exon 5 of 9	ENSP00000378109.2	Q9NQC3-6

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152090 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000116 AC: 29 AN: 250942 AF XY: 0.0000885

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000708

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000527 AC: 77 AN: 1461378 Hom.: 0 Cov.: 30 AF XY: 0.0000481 AC XY: 35 AN XY: 726956

African (AFR) AF: 0.000269 AC: 9 AN: 33452

American (AMR) AF: 0.000224 AC: 10 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00113 AC: 45 AN: 39664

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111798

Other (OTH) AF: 0.0000497 AC: 3 AN: 60368

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152206 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 12 AN XY: 74424

African (AFR) AF: 0.000265 AC: 11 AN: 41520

American (AMR) AF: 0.000458 AC: 7 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000657 Hom.: 0

Bravo AF: 0.000249

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000824 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.22
Sift	Benign	0.055	T
Sift4G	Benign	0.10	T
Polyphen		0.98	D
Vest4		0.52
MVP		0.67
MPC		0.17
ClinPred		0.33	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.71
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

dbSNP: rs142622923; hg19: chr2-55209706;