chr1-43936385-C-G

Variant names:

• chr1-43936385-C-G
• rs2085096564
• NM_057091.3:c.283C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_057091.3(ARTN):​c.283C>G​(p.Pro95Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000666 in 150,062 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. 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. P95S) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
• Consequence: ARTN NM_057091.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12676942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARTN	NM_057091.3	c.283C>G	p.Pro95Ala	missense_variant	Exon 5 of 5	ENST00000372359.10	NP_476432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARTN	ENST00000372359.10	c.283C>G	p.Pro95Ala	missense_variant	Exon 5 of 5	1	NM_057091.3	ENSP00000361434.5

Frequencies

GnomAD3 genomes AF: 0.00000666 AC: 1 AN: 150062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000666 AC: 1 AN: 150062 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73182

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000663

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.13	.;T;.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.36	T;.;.;T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.7	.;L;.;L;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.16	N;N;N;N;N
REVEL	Benign	0.099
Sift	Uncertain	0.028	D;D;D;D;D
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0040	B;B;B;B;B
Vest4		0.19
MutPred		0.36		.;Loss of glycosylation at P95 (P = 0.0013);.;Loss of glycosylation at P95 (P = 0.0013);.;
MVP		0.64
MPC		2.7
ClinPred		0.073	T
GERP RS		-1.1
Varity_R		0.043
gMVP		0.30

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

Other links and lift over

dbSNP: rs2085096564; hg19: chr1-44402057;