1-107324465-C-T

Variant names:

• chr1-107324465-C-T
• rs151288291
• NM_001113226.3:c.430C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001113226.3(NTNG1):​c.430C>T​(p.Leu144Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000595 in 1,613,778 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: 0.00030 (2 hom.)
• Consequence: NTNG1 NM_001113226.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 5.04
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 1-107324465-C-T is Benign according to our data. Variant chr1-107324465-C-T is described in ClinVar as Benign. ClinVar VariationId is 715245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 518 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.430C>T	p.Leu144Leu	synonymous	Exon 3 of 8	NP_001106697.1	Q9Y2I2-3
	NTNG1	NM_001372167.1		c.430C>T	p.Leu144Leu	synonymous	Exon 3 of 8	NP_001359096.1	Q9Y2I2-3
	NTNG1	NM_001372170.1		c.430C>T	p.Leu144Leu	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.430C>T	p.Leu144Leu	synonymous	Exon 3 of 8	ENSP00000359085.1	Q9Y2I2-3
	NTNG1	ENST00000370066.5	TSL:1	c.430C>T	p.Leu144Leu	synonymous	Exon 2 of 7	ENSP00000359083.1	Q9Y2I2-4
	NTNG1	ENST00000370074.8	TSL:1	c.430C>T	p.Leu144Leu	synonymous	Exon 3 of 6	ENSP00000359091.3	Q9Y2I2-1

Frequencies

GnomAD3 genomes AF: 0.00341 AC: 519 AN: 152040 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00106 AC: 265 AN: 250156 AF XY: 0.000696

Gnomad AFR exome AF: 0.0143

Gnomad AMR exome AF: 0.000725

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000302 AC: 442 AN: 1461620 Hom.: 2 Cov.: 33 AF XY: 0.000267 AC XY: 194 AN XY: 727118

African (AFR) AF: 0.0103 AC: 343 AN: 33458

American (AMR) AF: 0.000918 AC: 41 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111866

Other (OTH) AF: 0.000729 AC: 44 AN: 60384

GnomAD4 genome AF: 0.00340 AC: 518 AN: 152158 Hom.: 2 Cov.: 32 AF XY: 0.00308 AC XY: 229 AN XY: 74374

African (AFR) AF: 0.0119 AC: 493 AN: 41526

American (AMR) AF: 0.00118 AC: 18 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67996

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00180 Hom.: 0

Bravo AF: 0.00404

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	NTNG1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		5.0
Mutation Taster		=90/10	polymorphism

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: rs151288291; hg19: chr1-107867087;