rs757343656

Variant names:

• chr19-45488923-G-A
• rs757343656
• NM_005619.5:c.1305C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_005619.5(RTN2):​c.1305C>T​(p.Ile435Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000288 in 1,458,654 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: RTN2 NM_005619.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.76
• Publications: 0 publications found

Genes affected

RTN2 (HGNC:10468): (reticulon 2) 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. Reticulon proteins also play an important role in the replication of positive-strand RNA (ssRNA) viruses. Mutations at this locus have been associated with autosomal dominant spastic paraplegia-12. [provided by RefSeq, Aug 2020]

PPM1N (HGNC:26845): (protein phosphatase, Mg2+/Mn2+ dependent 1N (putative)) Predicted to enable metal ion binding activity and protein serine/threonine phosphatase activity. Predicted to be involved in negative regulation of I-kappaB kinase/NF-kappaB signaling and positive regulation of canonical Wnt signaling pathway. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 19-45488923-G-A is Benign according to our data. Variant chr19-45488923-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 697995.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005619.5. 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
	RTN2	NM_005619.5	MANE Select	c.1305C>T	p.Ile435Ile	synonymous	Exon 7 of 11	NP_005610.1	O75298-1
	RTN2	NM_206900.3		c.1086C>T	p.Ile362Ile	synonymous	Exon 6 of 10	NP_996783.1	O75298-2
	RTN2	NM_206901.3		c.285C>T	p.Ile95Ile	synonymous	Exon 3 of 7	NP_996784.1	O75298-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN2	ENST00000245923.9	TSL:1 MANE Select	c.1305C>T	p.Ile435Ile	synonymous	Exon 7 of 11	ENSP00000245923.3	O75298-1
	RTN2	ENST00000344680.8	TSL:1	c.1086C>T	p.Ile362Ile	synonymous	Exon 6 of 10	ENSP00000345127.3	O75298-2
	RTN2	ENST00000430715.6	TSL:1	c.285C>T	p.Ile95Ile	synonymous	Exon 3 of 7	ENSP00000398178.1	O75298-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000826 AC: 2 AN: 242180 AF XY: 0.00000764

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000288 AC: 42 AN: 1458654 Hom.: 0 Cov.: 33 AF XY: 0.0000262 AC XY: 19 AN XY: 725256

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.00 AC: 0 AN: 85422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1110842

Other (OTH) AF: 0.00 AC: 0 AN: 60268

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.62
DANN	Benign	0.87
PhyloP100		-2.8
PromoterAI		-0.021	Neutral

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

Other links and lift over

dbSNP: rs757343656; hg19: chr19-45992181;