chr16-2471981-C-A

Variant names:

• chr16-2471981-C-A
• rs749265175
• NM_006181.3:c.280C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006181.3(NTN3):​c.280C>A​(p.Arg94Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000622 in 1,445,832 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R94C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: NTN3 NM_006181.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.67
• Publications: 2 publications found

Genes affected

NTN3 (HGNC:8030): (netrin 3) Predicted to enable signaling receptor binding activity. Predicted to be involved in animal organ morphogenesis; neuron projection development; and tissue development. Predicted to be located in Golgi apparatus and extracellular region. Predicted to be active in basement membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006181.3. 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
	NTN3	NM_006181.3	MANE Select	c.280C>A	p.Arg94Ser	missense	Exon 1 of 6	NP_006172.1	O00634

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTN3	ENST00000293973.2	TSL:1 MANE Select	c.280C>A	p.Arg94Ser	missense	Exon 1 of 6	ENSP00000293973.1	O00634

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000871 AC: 2 AN: 229536 AF XY: 0.0000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000622 AC: 9 AN: 1445832 Hom.: 0 Cov.: 33 AF XY: 0.0000111 AC XY: 8 AN XY: 719358

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25914

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.00 AC: 0 AN: 85742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000811 AC: 9 AN: 1109800

Other (OTH) AF: 0.00 AC: 0 AN: 60034

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000167 AC: 2

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Benign	-0.0043
Eigen_PC	Benign	0.0024
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.81	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.7
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.47
Sift	Benign	0.052	T
Sift4G	Benign	0.083	T
Polyphen		0.32	B
Vest4		0.48
MutPred		0.68		Gain of phosphorylation at R94 (P = 0.0502)
MVP		0.81
MPC		0.70
ClinPred		0.81	D
GERP RS		3.6
Varity_R		0.19
gMVP		0.70
Mutation Taster		=42/58	disease causing

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: rs749265175; hg19: chr16-2521982;