NM_021136.3:c.1850A>G

Variant names:

• chr14-59607408-T-C
• NM_021136.3:c.1850A>G

Variant summary

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

The NM_021136.3(RTN1):​c.1850A>G​(p.Gln617Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RTN1 NM_021136.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.25

Genes affected

RTN1 (HGNC:10467): (reticulon 1) 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. This gene is considered to be a specific marker for neurological diseases and cancer, and is a potential molecular target for therapy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN1	NM_021136.3	c.1850A>G	p.Gln617Arg	missense_variant	Exon 4 of 9	ENST00000267484.10	NP_066959.1
RTN1	NM_206852.3	c.146A>G	p.Gln49Arg	missense_variant	Exon 2 of 7		NP_996734.1
RTN1	NM_001363702.1	c.101A>G	p.Gln34Arg	missense_variant	Exon 2 of 7		NP_001350631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN1	ENST00000267484.10	c.1850A>G	p.Gln617Arg	missense_variant	Exon 4 of 9	1	NM_021136.3	ENSP00000267484.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461702 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T;.;T;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.3	.;.;M;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.4	N;N;N;.
REVEL	Benign	0.29
Sift	Benign	0.32	T;T;D;.
Sift4G	Benign	0.34	T;T;T;T
Polyphen		0.47	P;B;D;.
Vest4		0.72
MutPred		0.58		.;.;Gain of methylation at Q617 (P = 0.0858);.;
MVP		0.26
MPC		1.8
ClinPred		0.96	D
GERP RS		6.0
Varity_R		0.48
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-60074126;