1-43936356-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_057091.3(ARTN):​c.254C>T​(p.Pro85Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,157,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ARTN
NM_057091.3 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09089205).
BS2
High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARTNNM_057091.3 linkc.254C>T p.Pro85Leu missense_variant Exon 5 of 5 ENST00000372359.10 NP_476432.2 Q5T4W7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARTNENST00000372359.10 linkc.254C>T p.Pro85Leu missense_variant Exon 5 of 5 1 NM_057091.3 ENSP00000361434.5 Q5T4W7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000164
AC:
19
AN:
1157596
Hom.:
0
Cov.:
32
AF XY:
0.0000161
AC XY:
9
AN XY:
557710
show subpopulations
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:
0.0000186
Gnomad4 OTH exome
AF:
0.0000212
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.278C>T (p.P93L) alteration is located in exon 5 (coding exon 3) of the ARTN gene. This alteration results from a C to T substitution at nucleotide position 278, causing the proline (P) at amino acid position 93 to be replaced by a leucine (L). 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
0.12
BayesDel_addAF
Benign
-0.055
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
14
DANN
Benign
0.94
DEOGEN2
Benign
0.11
.;T;.;T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.58
T;.;.;T;T
M_CAP
Pathogenic
0.40
D
MetaRNN
Benign
0.091
T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.4
.;L;.;L;.
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.42
N;N;N;N;N
REVEL
Benign
0.082
Sift
Benign
0.047
D;D;D;D;D
Sift4G
Uncertain
0.023
D;D;D;D;D
Polyphen
0.0020
B;B;B;B;B
Vest4
0.15
MutPred
0.22
.;Loss of glycosylation at P85 (P = 0.0078);.;Loss of glycosylation at P85 (P = 0.0078);.;
MVP
0.53
MPC
2.3
ClinPred
0.15
T
GERP RS
0.94
Varity_R
0.039
gMVP
0.21

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

LitVar

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

Other links and lift over

dbSNP: rs1211771400; hg19: chr1-44402028; API