chr1-107324724-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001113226.3(NTNG1):​c.689C>T​(p.Ala230Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NTNG1
NM_001113226.3 missense

Scores

6
11
2

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
NTNG1 (HGNC:23319): (netrin G1) This gene encodes a preproprotein that is processed into a secreted protein containing eukaroytic growth factor (EGF)-like domains. This protein acts to guide axon growth during neuronal development. Polymorphisms in this gene may be associated with schizophrenia. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2015]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTNG1NM_001113226.3 linkc.689C>T p.Ala230Val missense_variant Exon 3 of 8 ENST00000370068.6 NP_001106697.1 Q9Y2I2-3Q5IEC8Q5IEC3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTNG1ENST00000370068.6 linkc.689C>T p.Ala230Val missense_variant Exon 3 of 8 5 NM_001113226.3 ENSP00000359085.1 Q9Y2I2-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
249732
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134936
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461336
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
726982
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not provided Uncertain:1
-
Richard Lifton Laboratory, Yale University School of Medicine
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.44
.;T;.;T;.;.;.
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
D;D;D;.;D;.;D
M_CAP
Benign
0.064
D
MetaRNN
Pathogenic
0.80
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.080
D
MutationAssessor
Uncertain
2.4
M;M;M;M;M;M;M
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-2.5
N;N;D;N;N;N;N
REVEL
Uncertain
0.40
Sift
Uncertain
0.0020
D;D;D;D;D;D;D
Sift4G
Uncertain
0.0090
D;D;D;D;D;D;D
Polyphen
1.0
D;D;D;D;.;D;.
Vest4
0.79
MutPred
0.62
Loss of catalytic residue at A230 (P = 0.0085);Loss of catalytic residue at A230 (P = 0.0085);Loss of catalytic residue at A230 (P = 0.0085);Loss of catalytic residue at A230 (P = 0.0085);Loss of catalytic residue at A230 (P = 0.0085);Loss of catalytic residue at A230 (P = 0.0085);Loss of catalytic residue at A230 (P = 0.0085);
MVP
0.84
MPC
1.7
ClinPred
0.97
D
GERP RS
6.0
Varity_R
0.37
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs386352339; hg19: chr1-107867346; COSMIC: COSV53976121; API