Variant 1-43936688-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_057091.3(ARTN):c.586G>A(p.Val196Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARTN
NM_057091.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.40

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2606706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARTN	NM_057091.3 linkuse as main transcript	c.586G>A	p.Val196Ile	missense_variant	5/5	ENST00000372359.10	NP_476432.2	Q5T4W7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARTN	ENST00000372359.10 linkuse as main transcript	c.586G>A	p.Val196Ile	missense_variant	5/5	1	NM_057091.3	ENSP00000361434.5		Q5T4W7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1444888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717818

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 23, 2023

The c.610G>A (p.V204I) alteration is located in exon 5 (coding exon 3) of the ARTN gene. This alteration results from a G to A substitution at nucleotide position 610, causing the valine (V) at amino acid position 204 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.0045

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

.;T;.;T;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.73

T;.;.;T;T

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.26

T;T;T;T;T

MetaSVM

Uncertain

-0.041

MutationAssessor

Benign

1.5

.;L;.;L;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.59

N;N;N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.12

T;T;T;T;T

Sift4G

Benign

0.091

T;T;T;T;T

Polyphen

0.28

B;P;B;P;P

Vest4

0.33

MutPred

0.45

.;Loss of catalytic residue at V196 (P = 0.0437);.;Loss of catalytic residue at V196 (P = 0.0437);.;

MVP

0.93

MPC

2.5

ClinPred

0.86

GERP RS

4.1

Varity_R

0.15

gMVP

0.53

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over