1-43936448-C-T

Variant names:

• chr1-43936448-C-T
• rs2085098030
• NM_057091.3:c.346C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_057091.3(ARTN):​c.346C>T​(p.Arg116Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R116G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARTN NM_057091.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2994061).

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.346C>T	p.Arg116Trp	missense	Exon 5 of 5	NP_476432.2	Q5T4W7-1
	ARTN	NM_001136215.2		c.370C>T	p.Arg124Trp	missense	Exon 4 of 4	NP_001129687.1	Q5T4W7-3
	ARTN	NM_057090.3		c.370C>T	p.Arg124Trp	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.346C>T	p.Arg116Trp	missense	Exon 5 of 5	ENSP00000361434.5	Q5T4W7-1
	ARTN	ENST00000438616.3	TSL:1	c.397C>T	p.Arg133Trp	missense	Exon 2 of 2	ENSP00000391998.3	Q5T4W7-2
	ARTN	ENST00000498139.6	TSL:1	c.370C>T	p.Arg124Trp	missense	Exon 4 of 4	ENSP00000436727.1	Q5T4W7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1003384 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 472472

African (AFR) AF: 0.00 AC: 0 AN: 20156

American (AMR) AF: 0.00 AC: 0 AN: 5818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10926

East Asian (EAS) AF: 0.00 AC: 0 AN: 19042

South Asian (SAS) AF: 0.00 AC: 0 AN: 18860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2490

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 871008

Other (OTH) AF: 0.00 AC: 0 AN: 38030

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.55
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.017	D
Polyphen		0.13	B
Vest4		0.25
MutPred		0.39		Loss of methylation at R116 (P = 0.0013)
MVP		0.83
MPC		2.2
ClinPred		0.98	D
GERP RS		1.6
Varity_R		0.28
gMVP		0.37
Mutation Taster		=71/29	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: rs2085098030; hg19: chr1-44402120;