Variant 1-43936531-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_057091.3(ARTN):c.429G>C(p.Glu143Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000116 in 1,506,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ARTN
NM_057091.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.11

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARTN	NM_057091.3 linkuse as main transcript	c.429G>C	p.Glu143Asp	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.429G>C	p.Glu143Asp	missense_variant	5/5	1	NM_057091.3	ENSP00000361434.5		Q5T4W7-1

Frequencies

GnomAD3 genomes

AF:

0.0000989

AC:

AN:

151738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000571

AC:

AN:

104998

Hom.:

AF XY:

0.0000678

AC XY:

AN XY:

58978

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000481

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000117

AC:

159

AN:

1354228

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

668450

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000307

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:

0.000145

Gnomad4 OTH exome

AF:

0.0000712

GnomAD4 genome

AF:

0.0000988

AC:

AN:

151846

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000281

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000425

AC:

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

Nov 08, 2022

The c.453G>C (p.E151D) alteration is located in exon 5 (coding exon 3) of the ARTN gene. This alteration results from a G to C substitution at nucleotide position 453, causing the glutamic acid (E) at amino acid position 151 to be replaced by an aspartic acid (D). 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

Pathogenic

0.96

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

.;D;.;D;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.68

T;.;.;T;T

M_CAP

Pathogenic

0.79

MetaRNN

Uncertain

0.72

D;D;D;D;D

MetaSVM

Uncertain

0.41

MutationAssessor

Uncertain

2.7

.;M;.;M;.

PrimateAI

Pathogenic

0.97

PROVEAN

Uncertain

-2.6

D;D;D;D;D

REVEL

Pathogenic

0.73

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Uncertain

0.044

D;D;D;D;T

Polyphen

0.83

P;D;P;D;D

Vest4

0.58

MutPred

0.54

.;Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);.;

MVP

0.90

MPC

2.4

ClinPred

0.52

GERP RS

3.4

Varity_R

0.97

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over