Variant 1-43935685-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000372359.10(ARTN):c.29C>A(p.Thr10Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,064 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T10M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ARTN
ENST00000372359.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.329

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08947134).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARTN	NM_057091.3 linkuse as main transcript	c.29C>A	p.Thr10Lys	missense_variant	3/5	ENST00000372359.10	NP_476432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARTN	ENST00000372359.10 linkuse as main transcript	c.29C>A	p.Thr10Lys	missense_variant	3/5	1	NM_057091.3	ENSP00000361434	P1	Q5T4W7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461064

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726786

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:

0.00000900

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jun 04, 2024

The c.29C>A (p.T10K) alteration is located in exon 3 (coding exon 1) of the ARTN gene. This alteration results from a C to A substitution at nucleotide position 29, causing the threonine (T) at amino acid position 10 to be replaced by a lysine (K). 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

0.16

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Benign

7.8

DANN

Benign

0.68

DEOGEN2

Benign

0.091

.;T;.;.;.;.;.;.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.34

T;.;.;T;.;.;.;T;T;T

M_CAP

Benign

0.081

MetaRNN

Benign

0.089

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.0

N;N;.;.;N;.;.;.;.;N

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.50

N;N;D;D;N;D;D;D;D;N

REVEL

Benign

0.10

Sift

Uncertain

0.013

D;D;D;D;D;D;D;D;D;D

Sift4G

Benign

0.69

T;T;T;T;T;D;T;T;D;T

Polyphen

0.16

B;B;.;.;B;.;.;.;.;B

Vest4

0.23

MutPred

0.28

Gain of ubiquitination at T10 (P = 0.0138);Gain of ubiquitination at T10 (P = 0.0138);Gain of ubiquitination at T10 (P = 0.0138);Gain of ubiquitination at T10 (P = 0.0138);Gain of ubiquitination at T10 (P = 0.0138);Gain of ubiquitination at T10 (P = 0.0138);Gain of ubiquitination at T10 (P = 0.0138);Gain of ubiquitination at T10 (P = 0.0138);Gain of ubiquitination at T10 (P = 0.0138);Gain of ubiquitination at T10 (P = 0.0138);

MVP

0.77

MPC

0.0048

ClinPred

0.091

GERP RS

-2.1

Varity_R

0.12

gMVP

0.22

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.

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