14-59745807-T-C

Variant names:

• chr14-59745807-T-C
• rs758276986
• NM_021136.3:c.916A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021136.3(RTN1):​c.916A>G​(p.Ile306Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RTN1 NM_021136.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04144475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN1	NM_021136.3	c.916A>G	p.Ile306Val	missense_variant	Exon 2 of 9	ENST00000267484.10	NP_066959.1
RTN1	XM_011537063.4	c.916A>G	p.Ile306Val	missense_variant	Exon 2 of 4		XP_011535365.1
RTN1	XM_047431674.1	c.916A>G	p.Ile306Val	missense_variant	Exon 2 of 4		XP_047287630.1
RTN1	XR_007064042.1	n.1062A>G		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN1	ENST00000267484.10	c.916A>G	p.Ile306Val	missense_variant	Exon 2 of 9	1	NM_021136.3	ENSP00000267484.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727242

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

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	0.069
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.0
DANN	Benign	0.72
DEOGEN2	Benign	0.0042	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.75	N;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.010	N;.
REVEL	Benign	0.014
Sift	Benign	0.52	T;.
Sift4G	Benign	0.82	T;T
Polyphen		0.0	B;.
Vest4		0.082
MutPred		0.22		Gain of glycosylation at S311 (P = 0.1421);.;
MVP		0.043
MPC		0.084
ClinPred		0.030	T
GERP RS		-1.8
Varity_R		0.030
gMVP		0.063

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs758276986; hg19: chr14-60212525;