chr4-121036811-AT-A
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_024574.4(NDNF):c.1159del(p.Ile387SerfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
NDNF
NM_024574.4 frameshift
NM_024574.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.905
Genes affected
NDNF (HGNC:26256): (neuron derived neurotrophic factor) Predicted to enable heparin binding activity. Involved in several processes, including cellular response to hypoxia; negative regulation of apoptotic process; and nitric oxide mediated signal transduction. Located in extracellular space. Implicated in hypogonadotropic hypogonadism. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.321 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 4-121036811-AT-A is Pathogenic according to our data. Variant chr4-121036811-AT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1709811.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDNF | NM_024574.4 | c.1159del | p.Ile387SerfsTer3 | frameshift_variant | 4/4 | ENST00000379692.9 | |
NDNF | XM_024454212.2 | c.1159del | p.Ile387SerfsTer3 | frameshift_variant | 4/4 | ||
NDNF | XM_024454213.2 | c.1159del | p.Ile387SerfsTer3 | frameshift_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDNF | ENST00000379692.9 | c.1159del | p.Ile387SerfsTer3 | frameshift_variant | 4/4 | 1 | NM_024574.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 67
GnomAD4 exome
Cov.:
67
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypogonadotropic hypogonadism 25 with anosmia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | Aug 13, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.