1-107324399-A-G

Variant names:

• chr1-107324399-A-G
• rs1667826703
• NM_001113226.3:c.364A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001113226.3(NTNG1):​c.364A>G​(p.Thr122Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000171 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: NTNG1 NM_001113226.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.49
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 25 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.364A>G	p.Thr122Ala	missense	Exon 3 of 8	NP_001106697.1	Q9Y2I2-3
	NTNG1	NM_001372167.1		c.364A>G	p.Thr122Ala	missense	Exon 3 of 8	NP_001359096.1	Q9Y2I2-3
	NTNG1	NM_001372170.1		c.364A>G	p.Thr122Ala	missense	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.364A>G	p.Thr122Ala	missense	Exon 3 of 8	ENSP00000359085.1	Q9Y2I2-3
	NTNG1	ENST00000370066.5	TSL:1	c.364A>G	p.Thr122Ala	missense	Exon 2 of 7	ENSP00000359083.1	Q9Y2I2-4
	NTNG1	ENST00000370074.8	TSL:1	c.364A>G	p.Thr122Ala	missense	Exon 3 of 6	ENSP00000359091.3	Q9Y2I2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461644 Hom.: 0 Cov.: 33 AF XY: 0.0000193 AC XY: 14 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111836

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.72	P
Vest4		0.47
MutPred		0.54		Gain of catalytic residue at T122 (P = 0.015)
MVP		0.82
MPC		1.3
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.66
gMVP		0.52
Mutation Taster		=50/50

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: rs1667826703; hg19: chr1-107867021;