1-43935669-CTT-GTA

Variant names:

• chr1-43935669-CTT-GTA
• NM_057091.3:c.13_15delCTTinsGTA
• ARTN p.Leu5Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_057091.3(ARTN):​c.13_15delCTTinsGTA​(p.Leu5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARTN NM_057091.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• 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 0 ACMG points.

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.13_15delCTTinsGTA	p.Leu5Val	missense	N/A	NP_476432.2	Q5T4W7-1
	ARTN	NM_001136215.2		c.13_15delCTTinsGTA	p.Leu5Val	missense	N/A	NP_001129687.1	Q5T4W7-3
	ARTN	NM_057090.3		c.13_15delCTTinsGTA	p.Leu5Val	missense	N/A	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.13_15delCTTinsGTA	p.Leu5Val	missense	N/A	ENSP00000361434.5	Q5T4W7-1
	ARTN	ENST00000498139.6	TSL:1	c.13_15delCTTinsGTA	p.Leu5Val	missense	N/A	ENSP00000436727.1	Q5T4W7-3
	ARTN	ENST00000372354.3	TSL:1	c.13_15delCTTinsGTA	p.Leu5Val	missense	N/A	ENSP00000361429.3	Q5T4W7-1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.030

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-44401341;