Variant rs79744308 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004558.5(NRTN):c.175G>A(p.Ala59Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,218,970 control chromosomes in the GnomAD database, including 1,520 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 264 hom., cov: 31)

Exomes 𝑓: 0.045 ( 1256 hom. )

Consequence

NRTN
NM_004558.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.97

Variant links:

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]

NRTN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011277497).

BP6

Variant 19-5827754-G-A is Benign according to our data. Variant chr19-5827754-G-A is described in ClinVar as [Benign]. Clinvar id is 259427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRTN	NM_004558.5 link	c.175G>A	p.Ala59Thr	missense_variant	3/3	ENST00000303212.3	NP_004549.1	Q99748
NRTN	XM_047438890.1 link	c.175G>A	p.Ala59Thr	missense_variant	2/2		XP_047294846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRTN	ENST00000303212.3 link	c.175G>A	p.Ala59Thr	missense_variant	3/3	1	NM_004558.5	ENSP00000302648.1		Q99748

Frequencies

GnomAD3 genomes

AF:

0.0534

AC:

8068

AN:

151134

Hom.:

266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0707

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.0428

Gnomad ASJ

AF:

0.0670

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.0281

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0396

Gnomad OTH

AF:

0.0612

GnomAD3 exomes

AF:

0.0451

AC:

2566

AN:

56878

Hom.:

AF XY:

0.0467

AC XY:

1513

AN XY:

32426

show subpopulations

Gnomad AFR exome

AF:

0.0664

Gnomad AMR exome

AF:

0.0234

Gnomad ASJ exome

AF:

0.0421

Gnomad EAS exome

AF:

0.0864

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.0278

Gnomad NFE exome

AF:

0.0363

Gnomad OTH exome

AF:

0.0421

GnomAD4 exome

AF:

0.0446

AC:

47657

AN:

1067722

Hom.:

1256

Cov.:

AF XY:

0.0448

AC XY:

22832

AN XY:

509236

show subpopulations

Gnomad4 AFR exome

AF:

0.0689

Gnomad4 AMR exome

AF:

0.0270

Gnomad4 ASJ exome

AF:

0.0618

Gnomad4 EAS exome

AF:

0.0667

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.0237

Gnomad4 NFE exome

AF:

0.0412

Gnomad4 OTH exome

AF:

0.0550

GnomAD4 genome

AF:

0.0534

AC:

8079

AN:

151248

Hom.:

264

Cov.:

AF XY:

0.0544

AC XY:

4020

AN XY:

73954

show subpopulations

Gnomad4 AFR

AF:

0.0707

Gnomad4 AMR

AF:

0.0428

Gnomad4 ASJ

AF:

0.0670

Gnomad4 EAS

AF:

0.103

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.0281

Gnomad4 NFE

AF:

0.0396

Gnomad4 OTH

AF:

0.0649

Alfa

AF:

0.0434

Hom.:

Bravo

AF:

0.0525

TwinsUK

AF:

0.0469

AC:

174

ALSPAC

AF:

0.0449

AC:

173

ESP6500AA

AF:

0.0431

AC:

113

ESP6500EA

AF:

0.0350

AC:

180

ExAC

AF:

0.0423

AC:

4442

Asia WGS

AF:

0.164

AC:

569

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0011

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.10

REVEL

Benign

0.19

Sift

Uncertain

0.022

Sift4G

Benign

0.17

Polyphen

0.44

Vest4

0.022

MPC

1.5

ClinPred

0.011

GERP RS

4.1

Varity_R

0.099

gMVP

0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over