NM_001113226.3:c.246+30116C>A

Variant names:

• chr1-107178955-C-A
• rs5023291
• NM_001113226.3:c.246+30116C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001113226.3(NTNG1):​c.246+30116C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,132 control chromosomes in the GnomAD database, including 49,693 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (49693 hom., cov: 32)
• Consequence: NTNG1 NM_001113226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 2 publications found

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]

NTNG1 Gene-Disease associations (from GenCC):

• atypical Rett syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113226.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTNG1	NM_001113226.3	MANE Select	c.246+30116C>A		intron	N/A	NP_001106697.1
	NTNG1	NM_001372167.1		c.246+30116C>A		intron	N/A	NP_001359096.1
	NTNG1	NM_001372170.1		c.246+30116C>A		intron	N/A	NP_001359099.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTNG1	ENST00000370068.6	TSL:5 MANE Select	c.246+30116C>A		intron	N/A	ENSP00000359085.1
	NTNG1	ENST00000370066.5	TSL:1	c.246+30116C>A		intron	N/A	ENSP00000359083.1
	NTNG1	ENST00000370074.8	TSL:1	c.246+30116C>A		intron	N/A	ENSP00000359091.3

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122686 AN: 152014 Hom.: 49662 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.821

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.807 AC: 122767 AN: 152132 Hom.: 49693 Cov.: 32 AF XY: 0.805 AC XY: 59848 AN XY: 74366

African (AFR) AF: 0.747 AC: 30974 AN: 41472

American (AMR) AF: 0.762 AC: 11647 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3018 AN: 3472

East Asian (EAS) AF: 0.817 AC: 4221 AN: 5164

South Asian (SAS) AF: 0.800 AC: 3854 AN: 4816

European-Finnish (FIN) AF: 0.831 AC: 8804 AN: 10598

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57488 AN: 68012

Other (OTH) AF: 0.822 AC: 1739 AN: 2116

Alfa AF: 0.823 Hom.: 6684

Bravo AF: 0.799

Asia WGS AF: 0.786 AC: 2733 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.64
DANN	Benign	0.63
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5023291; hg19: chr1-107721577;