1-43936214-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.182C>T​(p.Pro61Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000924 in 1,483,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

ARTN
NM_057091.3 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.579
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=0.22317281).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARTNNM_057091.3 linkc.182C>T p.Pro61Leu missense_variant Exon 4 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.182C>T p.Pro61Leu missense_variant Exon 4 of 5 1 NM_057091.3 ENSP00000361434.5 Q5T4W7-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152094
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000732
AC:
6
AN:
81918
Hom.:
0
AF XY:
0.0000440
AC XY:
2
AN XY:
45506
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000619
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:
0.000153
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000992
AC:
132
AN:
1331180
Hom.:
0
Cov.:
32
AF XY:
0.000109
AC XY:
71
AN XY:
654182
show subpopulations
Gnomad4 AFR exome
AF:
0.000108
Gnomad4 AMR exome
AF:
0.0000358
Gnomad4 ASJ exome
AF:
0.0000459
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000308
Gnomad4 NFE exome
AF:
0.000113
Gnomad4 OTH exome
AF:
0.000108
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152094
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453
ExAC
AF:
0.0000534
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.206C>T (p.P69L) alteration is located in exon 4 (coding exon 2) of the ARTN gene. This alteration results from a C to T substitution at nucleotide position 206, causing the proline (P) at amino acid position 69 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
0.11
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.15
.;T;.;.;.;.;.;.;.;T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.56
T;.;.;T;.;.;.;T;T;T;T
M_CAP
Pathogenic
0.88
D
MetaRNN
Benign
0.22
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.59
T
MutationAssessor
Benign
1.8
.;L;.;.;.;.;.;.;.;L;.
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-1.6
N;N;D;D;N;D;D;D;D;N;N
REVEL
Benign
0.11
Sift
Benign
0.088
T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.78
T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.087
B;B;.;.;B;.;.;.;.;B;B
Vest4
0.16
MutPred
0.15
.;Gain of MoRF binding (P = 0.06);Gain of MoRF binding (P = 0.06);Gain of MoRF binding (P = 0.06);.;.;.;.;.;Gain of MoRF binding (P = 0.06);.;
MVP
0.83
MPC
1.5
ClinPred
0.048
T
GERP RS
1.6
Varity_R
0.032
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs758433988; hg19: chr1-44401886; API