19-5828053-G-A

Variant names:

• chr19-5828053-G-A
• NM_004558.5:c.474G>A
• NRTN p.Arg158Arg

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004558.5(NRTN):​c.474G>A​(p.Arg158Arg) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. R158R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NRTN NM_004558.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601
• Publications: 0 publications found

Genes affected

NRTN (HGNC:8007): (neurturin) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein signals through the RET receptor tyrosine kinase and a GPI-linked coreceptor, and promotes survival of neuronal populations. A neurturin mutation has been described in a family with Hirschsprung Disease. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=0.601 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004558.5. 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
	NRTN	NM_004558.5	MANE Select	c.474G>A	p.Arg158Arg	synonymous	Exon 3 of 3	NP_004549.1	Q99748

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRTN	ENST00000303212.3	TSL:1 MANE Select	c.474G>A	p.Arg158Arg	synonymous	Exon 3 of 3	ENSP00000302648.1	Q99748
	NRTN	ENST00000879152.1		c.474G>A	p.Arg158Arg	synonymous	Exon 3 of 3	ENSP00000549211.1
	NRTN	ENST00000936080.1		c.474G>A	p.Arg158Arg	synonymous	Exon 3 of 3	ENSP00000606139.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1276680 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 627528

African (AFR) AF: 0.00 AC: 0 AN: 25466

American (AMR) AF: 0.00 AC: 0 AN: 18716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20676

East Asian (EAS) AF: 0.00 AC: 0 AN: 28230

South Asian (SAS) AF: 0.00 AC: 0 AN: 63560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3952

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1030952

Other (OTH) AF: 0.00 AC: 0 AN: 52822

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	11
DANN	Uncertain	0.98
PhyloP100		0.60

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

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

Other links and lift over

hg19: chr19-5828064;