rs1389830590

Variant names:

• chr1-43935669-C-G
• rs1389830590
• NM_057091.3:c.13C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-43935669-C-G
• chr1-43935669-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_057091.3(ARTN):​c.13C>G​(p.Leu5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARTN NM_057091.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0300
• Publications: 1 publications found

Genes affected

ARTN (HGNC:727): (artemin) This gene encodes a secreted ligand of the glial cell line-derived neurotrophic factor (GDNF) subfamily and TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein signals through the RET receptor and GFR alpha 3 coreceptor, and supports the survival of a number of peripheral neuron populations and at least one population of dopaminergic CNS neurons. This protein has also been shown to promote tumor growth, metastasis, and drug resistance in mammary carcinoma. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0869416).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_057091.3. 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
	ARTN	NM_057091.3	MANE Select	c.13C>G	p.Leu5Val	missense	Exon 3 of 5	NP_476432.2	Q5T4W7-1
	ARTN	NM_001136215.2		c.13C>G	p.Leu5Val	missense	Exon 2 of 4	NP_001129687.1	Q5T4W7-3
	ARTN	NM_057090.3		c.13C>G	p.Leu5Val	missense	Exon 3 of 5	NP_476431.2	Q5T4W7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARTN	ENST00000372359.10	TSL:1 MANE Select	c.13C>G	p.Leu5Val	missense	Exon 3 of 5	ENSP00000361434.5	Q5T4W7-1
	ARTN	ENST00000498139.6	TSL:1	c.13C>G	p.Leu5Val	missense	Exon 2 of 4	ENSP00000436727.1	Q5T4W7-3
	ARTN	ENST00000372354.3	TSL:1	c.13C>G	p.Leu5Val	missense	Exon 1 of 3	ENSP00000361429.3	Q5T4W7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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	0.076
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.030
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.047
Sift	Uncertain	0.014	D
Sift4G	Benign	0.20	T
Polyphen		0.56	P
Vest4		0.18
MutPred		0.21		Gain of relative solvent accessibility (P = 0.09)
MVP		0.78
MPC		0.0063
ClinPred		0.14	T
GERP RS		1.6
PromoterAI		-0.025	Neutral
Varity_R		0.13
gMVP		0.15
Mutation Taster		=96/4	polymorphism

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: rs1389830590; hg19: chr1-44401341;