1-107324617-G-C

Position:

• chr1-107324617-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001113226.3(NTNG1):​c.582G>C​(p.Lys194Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NTNG1 NM_001113226.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20459852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTNG1	NM_001113226.3	c.582G>C	p.Lys194Asn	missense_variant	3/8	ENST00000370068.6	NP_001106697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTNG1	ENST00000370068.6	c.582G>C	p.Lys194Asn	missense_variant	3/8	5	NM_001113226.3	ENSP00000359085.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.582G>C (p.K194N) alteration is located in exon 3 (coding exon 2) of the NTNG1 gene. This alteration results from a G to C substitution at nucleotide position 582, causing the lysine (K) at amino acid position 194 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T;.;T;.;.;.
Eigen	Benign	-0.0069
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D;D;.;D;.;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.99	L;L;L;L;L;L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.97	N;N;N;N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.063	T;T;T;T;T;T;T
Sift4G	Uncertain	0.020	D;T;D;T;D;D;T
Polyphen		0.0	B;B;B;B;.;B;.
Vest4		0.26
MutPred		0.37		Loss of ubiquitination at K194 (P = 0.0127);Loss of ubiquitination at K194 (P = 0.0127);Loss of ubiquitination at K194 (P = 0.0127);Loss of ubiquitination at K194 (P = 0.0127);Loss of ubiquitination at K194 (P = 0.0127);Loss of ubiquitination at K194 (P = 0.0127);Loss of ubiquitination at K194 (P = 0.0127);
MVP		0.73
MPC		0.79
ClinPred		0.64	D
GERP RS		6.0
Varity_R		0.38
gMVP		0.43

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-107867239;