Variant 19-5827869-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004558.5(NRTN):c.290G>A(p.Arg97Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000268 in 149,098 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NRTN
NM_004558.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRTN	NM_004558.5 linkuse as main transcript	c.290G>A	p.Arg97Gln	missense_variant	3/3	ENST00000303212.3
NRTN	XM_047438890.1 linkuse as main transcript	c.290G>A	p.Arg97Gln	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRTN	ENST00000303212.3 linkuse as main transcript	c.290G>A	p.Arg97Gln	missense_variant	3/3	1	NM_004558.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

149098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000598

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000363

AC:

AN:

1102656

Hom.:

Cov.:

AF XY:

0.00000187

AC XY:

AN XY:

533982

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000329

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000322

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000268

AC:

AN:

149098

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72654

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000598

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000102

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.290G>A (p.R97Q) alteration is located in exon 2 (coding exon 2) of the NRTN gene. This alteration results from a G to A substitution at nucleotide position 290, causing the arginine (R) at amino acid position 97 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Benign

0.11

Eigen_PC

Benign

0.068

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.97

MetaRNN

Uncertain

0.61

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.92

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.3

REVEL

Benign

0.23

Sift

Benign

0.10

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.19

MutPred

0.29

Loss of methylation at R97 (P = 0.0089);

MVP

0.87

MPC

1.7

ClinPred

0.95

GERP RS

4.2

Varity_R

0.53

gMVP

0.48

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