chr19-5828060-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004558.5(NRTN):āc.481G>Cā(p.Ala161Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000395 in 1,444,706 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.000043 ( 0 hom. )
Consequence
NRTN
NM_004558.5 missense
NM_004558.5 missense
Scores
2
10
7
Clinical Significance
Conservation
PhyloP100: 2.77
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]
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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 | c.481G>C | p.Ala161Pro | missense_variant | 3/3 | ENST00000303212.3 | |
NRTN | XM_047438890.1 | c.481G>C | p.Ala161Pro | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRTN | ENST00000303212.3 | c.481G>C | p.Ala161Pro | missense_variant | 3/3 | 1 | NM_004558.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000662 AC: 1AN: 150980Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000433 AC: 56AN: 1293726Hom.: 0 Cov.: 32 AF XY: 0.0000471 AC XY: 30AN XY: 636778
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GnomAD4 genome AF: 0.00000662 AC: 1AN: 150980Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73640
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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 | Aug 23, 2021 | The c.481G>C (p.A161P) alteration is located in exon 2 (coding exon 2) of the NRTN gene. This alteration results from a G to C substitution at nucleotide position 481, causing the alanine (A) at amino acid position 161 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0707);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at