NM_001265589.2:c.30C>T

Variant names:

• chr11-63681666-C-T
• rs11551949
• NM_001265589.2:c.30C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001265589.2(RTN3):​c.30C>T​(p.Ser10Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00953 in 1,611,502 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0097 (92 hom.)
• Consequence: RTN3 NM_001265589.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.269
• Publications: 5 publications found

Genes affected

RTN3 (HGNC:10469): (reticulon 3) This gene belongs to the reticulon family of highly conserved genes that are preferentially expressed in neuroendocrine tissues. This family of proteins interact with, and modulate the activity of beta-amyloid converting enzyme 1 (BACE1), and the production of amyloid-beta. An increase in the expression of any reticulon protein substantially reduces the production of amyloid-beta, suggesting that reticulon proteins are negative modulators of BACE1 in cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, and pseudogenes of this gene are located on chromosomes 4 and 12. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 11-63681666-C-T is Benign according to our data. Variant chr11-63681666-C-T is described in ClinVar as Benign. ClinVar VariationId is 777228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.269 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001265589.2. 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
	RTN3	NM_001265589.2	MANE Select	c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 9	NP_001252518.1	O95197-1
	RTN3	NM_201428.3		c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 8	NP_958831.1	O95197-2
	RTN3	NM_001265590.2		c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 8	NP_001252519.1	O95197-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN3	ENST00000377819.10	TSL:1 MANE Select	c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 9	ENSP00000367050.5	O95197-1
	RTN3	ENST00000339997.8	TSL:1	c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 8	ENSP00000344106.4	O95197-2
	RTN3	ENST00000540798.5	TSL:1	c.30C>T	p.Ser10Ser	synonymous	Exon 1 of 8	ENSP00000442733.1	O95197-7

Frequencies

GnomAD3 genomes AF: 0.00775 AC: 1180 AN: 152270 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00850

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00508

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00786 AC: 1950 AN: 247996 AF XY: 0.00785

Gnomad AFR exome AF: 0.00159

Gnomad AMR exome AF: 0.00547

Gnomad ASJ exome AF: 0.0264

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00572

Gnomad NFE exome AF: 0.0116

Gnomad OTH exome AF: 0.00677

GnomAD4 exome AF: 0.00972 AC: 14176 AN: 1459114 Hom.: 92 Cov.: 31 AF XY: 0.00946 AC XY: 6863 AN XY: 725696

African (AFR) AF: 0.00138 AC: 46 AN: 33326

American (AMR) AF: 0.00557 AC: 247 AN: 44382

Ashkenazi Jewish (ASJ) AF: 0.0227 AC: 592 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.000674 AC: 58 AN: 86038

European-Finnish (FIN) AF: 0.00626 AC: 333 AN: 53182

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5742

European-Non Finnish (NFE) AF: 0.0111 AC: 12345 AN: 1110598

Other (OTH) AF: 0.00901 AC: 543 AN: 60274

GnomAD4 genome AF: 0.00774 AC: 1179 AN: 152388 Hom.: 9 Cov.: 32 AF XY: 0.00696 AC XY: 519 AN XY: 74530

African (AFR) AF: 0.00224 AC: 93 AN: 41600

American (AMR) AF: 0.00849 AC: 130 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0230 AC: 80 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00508 AC: 54 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0117 AC: 796 AN: 68030

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.0101 Hom.: 4

Bravo AF: 0.00739

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0109

EpiControl AF: 0.0117

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		0.27
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs11551949; hg19: chr11-63449138;