rs61731573

Variant names:

• chr19-5824309-C-A
• rs61731573
• NM_004558.5:c.144C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-5824309-C-A
• chr19-5824309-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004558.5(NRTN):​c.144C>A​(p.Asp48Glu) variant causes a missense 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. 15/22 in silico tools predict 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. D48D) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NRTN NM_004558.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40796334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRTN	NM_004558.5	c.144C>A	p.Asp48Glu	missense_variant	Exon 2 of 3	ENST00000303212.3	NP_004549.1
NRTN	XM_047438890.1	c.144C>A	p.Asp48Glu	missense_variant	Exon 1 of 2		XP_047294846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRTN	ENST00000303212.3	c.144C>A	p.Asp48Glu	missense_variant	Exon 2 of 3	1	NM_004558.5	ENSP00000302648.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1454358 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723262

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 43866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.00 AC: 0 AN: 85248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110056

Other (OTH) AF: 0.00 AC: 0 AN: 60186

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.0046	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.0026
Eigen_PC	Benign	-0.077
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.18
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.27
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.86	T
Polyphen		0.99	D
Vest4		0.16
MutPred		0.34		Loss of MoRF binding (P = 0.1367);
MVP		0.92
MPC		0.70
ClinPred		0.46	T
GERP RS		0.83
Varity_R		0.086
gMVP		0.36
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61731573; hg19: chr19-5824320;