Genetic Variant ARTN:p.Arg116Gly (chr1-43936448-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_057091.3(ARTN):c.346C>G(p.Arg116Gly) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ARTN
NM_057091.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.547

Publications

0 publications found

Variant links:

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]

ARTN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.22604355).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARTN	NM_057091.3	MANE Select	c.346C>G	p.Arg116Gly	missense	Exon 5 of 5	NP_476432.2	Q5T4W7-1
ARTN	NM_001136215.2		c.370C>G	p.Arg124Gly	missense	Exon 4 of 4	NP_001129687.1	Q5T4W7-3
ARTN	NM_057090.3		c.370C>G	p.Arg124Gly	missense	Exon 5 of 5	NP_476431.2	Q5T4W7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARTN	ENST00000372359.10	TSL:1 MANE Select	c.346C>G	p.Arg116Gly	missense	Exon 5 of 5	ENSP00000361434.5	Q5T4W7-1
ARTN	ENST00000438616.3	TSL:1	c.397C>G	p.Arg133Gly	missense	Exon 2 of 2	ENSP00000391998.3	Q5T4W7-2
ARTN	ENST00000498139.6	TSL:1	c.370C>G	p.Arg124Gly	missense	Exon 4 of 4	ENSP00000436727.1	Q5T4W7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.36

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.41

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.76

PhyloP100

0.55

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.14

Sift

Benign

0.034

Sift4G

Benign

0.080

Polyphen

0.0020

Vest4

0.10

MutPred

0.36

Loss of methylation at R116 (P = 0.0013)

MVP

0.80

MPC

1.8

ClinPred

0.43

GERP RS

1.6

Varity_R

0.15

gMVP

0.38

Mutation Taster

=74/26

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over