Genetic Variant NM_057091.3:c.346C>A (chr1-43936448-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_057091.3(ARTN):c.346C>A(p.Arg116Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000997 in 1,003,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

ARTN
NM_057091.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.547

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=0.547 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARTN	NM_057091.3	MANE Select	c.346C>A	p.Arg116Arg	synonymous	Exon 5 of 5	NP_476432.2	Q5T4W7-1
ARTN	NM_001136215.2		c.370C>A	p.Arg124Arg	synonymous	Exon 4 of 4	NP_001129687.1	Q5T4W7-3
ARTN	NM_057090.3		c.370C>A	p.Arg124Arg	synonymous	Exon 5 of 5	NP_476431.2	Q5T4W7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARTN	ENST00000372359.10	TSL:1 MANE Select	c.346C>A	p.Arg116Arg	synonymous	Exon 5 of 5	ENSP00000361434.5	Q5T4W7-1
ARTN	ENST00000438616.3	TSL:1	c.397C>A	p.Arg133Arg	synonymous	Exon 2 of 2	ENSP00000391998.3	Q5T4W7-2
ARTN	ENST00000498139.6	TSL:1	c.370C>A	p.Arg124Arg	synonymous	Exon 4 of 4	ENSP00000436727.1	Q5T4W7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.97e-7

AC:

AN:

1003384

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

472472

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

20156

American (AMR)

AF:

0.00

AC:

AN:

5818

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10926

East Asian (EAS)

AF:

0.00

AC:

AN:

19042

South Asian (SAS)

AF:

0.0000530

AC:

AN:

18860

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2490

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

871008

Other (OTH)

AF:

0.00

AC:

AN:

38030

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.1

(source)

DANN

Benign

0.52

PhyloP100

0.55

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over