1-107324416-C-G

Variant names:

• chr1-107324416-C-G
• rs143347360
• NM_001113226.3:c.381C>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001113226.3(NTNG1):​c.381C>G​(p.Pro127Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00069 in 1,613,822 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (2 hom.)
• Consequence: NTNG1 NM_001113226.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.127
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 1-107324416-C-G is Benign according to our data. Variant chr1-107324416-C-G is described in ClinVar as Benign. ClinVar VariationId is 738290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.127 with no splicing effect.
• BS2: High AC in GnomAd4 at 521 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTNG1	NM_001113226.3	MANE Select	c.381C>G	p.Pro127Pro	synonymous	Exon 3 of 8	NP_001106697.1	Q9Y2I2-3
	NTNG1	NM_001372167.1		c.381C>G	p.Pro127Pro	synonymous	Exon 3 of 8	NP_001359096.1	Q9Y2I2-3
	NTNG1	NM_001372170.1		c.381C>G	p.Pro127Pro	synonymous	Exon 3 of 8	NP_001359099.1	Q9Y2I2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTNG1	ENST00000370068.6	TSL:5 MANE Select	c.381C>G	p.Pro127Pro	synonymous	Exon 3 of 8	ENSP00000359085.1	Q9Y2I2-3
	NTNG1	ENST00000370066.5	TSL:1	c.381C>G	p.Pro127Pro	synonymous	Exon 2 of 7	ENSP00000359083.1	Q9Y2I2-4
	NTNG1	ENST00000370074.8	TSL:1	c.381C>G	p.Pro127Pro	synonymous	Exon 3 of 6	ENSP00000359091.3	Q9Y2I2-1

Frequencies

GnomAD3 genomes AF: 0.00341 AC: 518 AN: 152060 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00101 AC: 252 AN: 250398 AF XY: 0.000695

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.000637

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000709

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000406 AC: 593 AN: 1461644 Hom.: 2 Cov.: 33 AF XY: 0.000316 AC XY: 230 AN XY: 727122

African (AFR) AF: 0.0138 AC: 461 AN: 33464

American (AMR) AF: 0.000604 AC: 27 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1111856

Other (OTH) AF: 0.00101 AC: 61 AN: 60384

GnomAD4 genome AF: 0.00342 AC: 521 AN: 152178 Hom.: 2 Cov.: 32 AF XY: 0.00327 AC XY: 243 AN XY: 74410

African (AFR) AF: 0.0122 AC: 508 AN: 41546

American (AMR) AF: 0.000328 AC: 5 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67992

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.00380

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	NTNG1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	10
DANN	Benign	0.69
PhyloP100		0.13
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs143347360; hg19: chr1-107867038;