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1-107324896-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001113226.3(NTNG1):c.861G>A(p.Ala287=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,612,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

NTNG1
NM_001113226.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.36
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 Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-107324896-G-A is Benign according to our data. Variant chr1-107324896-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3048525.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.36 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NTNG1NM_001113226.3 linkuse as main transcriptc.861G>A p.Ala287= synonymous_variant 3/8 ENST00000370068.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NTNG1ENST00000370068.6 linkuse as main transcriptc.861G>A p.Ala287= synonymous_variant 3/85 NM_001113226.3 P1Q9Y2I2-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000309
AC:
47
AN:
152046
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000618
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000218
AC:
54
AN:
248088
Hom.:
0
AF XY:
0.000261
AC XY:
35
AN XY:
134332
show subpopulations
Gnomad AFR exome
AF:
0.000126
Gnomad AMR exome
AF:
0.0000873
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000395
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.000221
AC:
323
AN:
1459966
Hom.:
0
Cov.:
33
AF XY:
0.000238
AC XY:
173
AN XY:
726124
show subpopulations
Gnomad4 AFR exome
AF:
0.0000898
Gnomad4 AMR exome
AF:
0.0000897
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000256
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000309
AC:
47
AN:
152164
Hom.:
0
Cov.:
32
AF XY:
0.000296
AC XY:
22
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.000618
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000459
Hom.:
1
Bravo
AF:
0.000348
EpiCase
AF:
0.000928
EpiControl
AF:
0.000831

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

NTNG1-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesDec 23, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
3.5
Dann
Benign
0.72

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.

Other links and lift over

dbSNP: rs142977353; hg19: chr1-107867518; COSMIC: COSV53962912; API