GeneBe

chr19-48661742-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145807.4(NTN5):​c.1405G>T​(p.Glu469*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,376,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

NTN5
NM_145807.4 stop_gained

Scores

2
2
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.240

Publications

0 publications found
Variant links:
Genes affected
NTN5 (HGNC:25208): (netrin 5) Predicted to enable signaling receptor binding activity. Predicted to be involved in animal organ morphogenesis; neuron projection development; and tissue development. Predicted to be located in extracellular region. Predicted to be active in basement membrane. [provided by Alliance of Genome Resources, Apr 2022]
SEC1P (HGNC:44149): (secretory blood group 1, pseudogene) Predicted to enable galactoside 2-alpha-L-fucosyltransferase activity. Predicted to act upstream of or within protein glycosylation. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTN5NM_145807.4 linkc.1405G>T p.Glu469* stop_gained Exon 7 of 7 ENST00000270235.11 NP_665806.1 Q8WTR8-1
SEC1PNR_004401.2 linkn.109-1455C>A intron_variant Intron 1 of 4
NTN5XM_011526443.4 linkc.*1435G>T downstream_gene_variant XP_011524745.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTN5ENST00000270235.11 linkc.1405G>T p.Glu469* stop_gained Exon 7 of 7 1 NM_145807.4 ENSP00000270235.4 Q8WTR8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.26e-7
AC:
1
AN:
1376724
Hom.:
0
Cov.:
34
AF XY:
0.00000146
AC XY:
1
AN XY:
684306
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
28296
American (AMR)
AF:
0.00
AC:
0
AN:
34998
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
32620
South Asian (SAS)
AF:
0.0000127
AC:
1
AN:
78996
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
35722
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5130
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1080814
Other (OTH)
AF:
0.00
AC:
0
AN:
56680
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.57
D
BayesDel_noAF
Pathogenic
0.58
CADD
Pathogenic
34
DANN
Uncertain
0.99
Eigen
Uncertain
0.29
Eigen_PC
Benign
0.051
FATHMM_MKL
Benign
0.66
D
PhyloP100
0.24
Vest4
0.041
GERP RS
0.27
Mutation Taster
=69/131
disease causing

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

Other links and lift over

dbSNP: rs998833186; hg19: chr19-49164999; API