chr19-5828053-G-T

Variant names:

• chr19-5828053-G-T
• rs7255720
• NM_004558.5:c.474G>T

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>T​(p.Arg158Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000783 in 1,276,680 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. Synonymous variant affecting the same amino acid position (i.e. R158R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• 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=-0.39).
• BP7: Synonymous conserved (PhyloP=0.601 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRTN	NM_004558.5	c.474G>T	p.Arg158Arg	synonymous_variant	Exon 3 of 3	ENST00000303212.3	NP_004549.1
NRTN	XM_047438890.1	c.474G>T	p.Arg158Arg	synonymous_variant	Exon 2 of 2		XP_047294846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRTN	ENST00000303212.3	c.474G>T	p.Arg158Arg	synonymous_variant	Exon 3 of 3	1	NM_004558.5	ENSP00000302648.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.83e-7 AC: 1 AN: 1276680 Hom.: 0 Cov.: 33 AF XY: 0.00000159 AC XY: 1 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: 0.0000157 AC: 1 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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	10
DANN	Benign	0.95
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

Other links and lift over

dbSNP: rs7255720; hg19: chr19-5828064;