NM_057091.3:c.254C>T

Variant names:

• chr1-43936356-C-T
• rs1211771400
• NM_057091.3:c.254C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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. 15/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_057091.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARTN	NM_057091.3	MANE Select	c.254C>T	p.Pro85Leu	missense	Exon 5 of 5	NP_476432.2	Q5T4W7-1
	ARTN	NM_001136215.2		c.278C>T	p.Pro93Leu	missense	Exon 4 of 4	NP_001129687.1	Q5T4W7-3
	ARTN	NM_057090.3		c.278C>T	p.Pro93Leu	missense	Exon 5 of 5	NP_476431.2	Q5T4W7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARTN	ENST00000372359.10	TSL:1 MANE Select	c.254C>T	p.Pro85Leu	missense	Exon 5 of 5	ENSP00000361434.5	Q5T4W7-1
	ARTN	ENST00000438616.3	TSL:1	c.305C>T	p.Pro102Leu	missense	Exon 2 of 2	ENSP00000391998.3	Q5T4W7-2
	ARTN	ENST00000498139.6	TSL:1	c.278C>T	p.Pro93Leu	missense	Exon 4 of 4	ENSP00000436727.1	Q5T4W7-3

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

African (AFR) AF: 0.00 AC: 0 AN: 23096

American (AMR) AF: 0.00 AC: 0 AN: 9306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15722

East Asian (EAS) AF: 0.00 AC: 0 AN: 26326

South Asian (SAS) AF: 0.00 AC: 0 AN: 39974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3168

European-Non Finnish (NFE) AF: 0.0000186 AC: 18 AN: 966826

Other (OTH) AF: 0.0000212 AC: 1 AN: 47068

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.082
Sift	Benign	0.047	D
Sift4G	Uncertain	0.023	D
Polyphen		0.0020	B
Vest4		0.15
MutPred		0.22		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
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs1211771400; hg19: chr1-44402028;