rs10494068

Variant names:

• chr1-107301888-G-A
• rs10494068
• NM_001113226.3:c.247-22394G>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.247-22394G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 152,152 control chromosomes in the GnomAD database, including 835 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 0.091 (835 hom., cov: 32)
• Consequence: NTNG1 NM_001113226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTNG1	NM_001113226.3	c.247-22394G>A		intron_variant	Intron 2 of 7	ENST00000370068.6	NP_001106697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTNG1	ENST00000370068.6	c.247-22394G>A		intron_variant	Intron 2 of 7	5	NM_001113226.3	ENSP00000359085.1

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13859 AN: 152034 Hom.: 832 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0933

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0740

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0679

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

GnomAD4 genome AF: 0.0912 AC: 13873 AN: 152152 Hom.: 835 Cov.: 32 AF XY: 0.0946 AC XY: 7040 AN XY: 74382

African (AFR) AF: 0.146 AC: 6061 AN: 41508

American (AMR) AF: 0.0936 AC: 1430 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3472

East Asian (EAS) AF: 0.196 AC: 1012 AN: 5168

South Asian (SAS) AF: 0.164 AC: 792 AN: 4824

European-Finnish (FIN) AF: 0.0740 AC: 783 AN: 10588

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0522 AC: 3549 AN: 67998

Other (OTH) AF: 0.0663 AC: 140 AN: 2112

Alfa AF: 0.0632 Hom.: 1719

Bravo AF: 0.0910

Asia WGS AF: 0.164 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.49
PhyloP100		0.15
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: rs10494068; hg19: chr1-107844510;