14-78730206-C-T

Variant names:

• chr14-78730206-C-T
• rs11159379
• NM_001330195.2:c.2044+15067C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330195.2(NRXN3):​c.2044+15067C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,966 control chromosomes in the GnomAD database, including 11,695 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (11695 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381
• Publications: 3 publications found

Genes affected

NRXN3 (HGNC:8010): (neurexin 3) This gene encodes a member of a family of proteins that function in the nervous system as receptors and cell adhesion molecules. Extensive alternative splicing and the use of alternative promoters results in multiple transcript variants and protein isoforms for this gene, but the full-length nature of many of these variants has not been determined. Transcripts that initiate from an upstream promoter encode alpha isoforms, which contain epidermal growth factor-like (EGF-like) sequences and laminin G domains. Transcripts initiating from the downstream promoter encode beta isoforms, which lack EGF-like sequences. Genetic variation at this locus has been associated with a range of behavioral phenotypes, including alcohol dependence and autism spectrum disorder. [provided by RefSeq, Dec 2012]

NRXN3 Gene-Disease associations (from GenCC):

• autism

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330195.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	NM_001330195.2	MANE Select	c.2044+15067C>T		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.2044+15067C>T		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.2056+15067C>T		intron	N/A	NP_001353355.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.2044+15067C>T		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.925+15067C>T		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000556496.2	TSL:1	n.1388+15067C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55180 AN: 151848 Hom.: 11701 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.392

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.363 AC: 55178 AN: 151966 Hom.: 11695 Cov.: 32 AF XY: 0.362 AC XY: 26900 AN XY: 74260

African (AFR) AF: 0.125 AC: 5201 AN: 41480

American (AMR) AF: 0.463 AC: 7060 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1679 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2179 AN: 5138

South Asian (SAS) AF: 0.341 AC: 1641 AN: 4816

European-Finnish (FIN) AF: 0.401 AC: 4238 AN: 10562

Middle Eastern (MID) AF: 0.466 AC: 135 AN: 290

European-Non Finnish (NFE) AF: 0.467 AC: 31744 AN: 67934

Other (OTH) AF: 0.391 AC: 826 AN: 2114

Alfa AF: 0.441 Hom.: 20352

Bravo AF: 0.360

Asia WGS AF: 0.362 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.77
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs11159379; hg19: chr14-79196549;