14-79417482-T-C

Variant names:

• chr14-79417482-T-C
• rs2217887
• NM_001330195.2:c.3263-49739T>C

Variant summary

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

The NM_001330195.2(NRXN3):​c.3263-49739T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,902 control chromosomes in the GnomAD database, including 8,221 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 0.32 (8221 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	NM_001330195.2	MANE Select	c.3263-49739T>C		intron	N/A	NP_001317124.1	A0A0A0MR89
	NRXN3	NM_001366425.1		c.3263-49739T>C		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.3275-49739T>C		intron	N/A	NP_001353355.1	A0A0U1RQC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.3263-49739T>C		intron	N/A	ENSP00000338349.7	A0A0A0MR89
	NRXN3	ENST00000554719.5	TSL:1	c.2144-49739T>C		intron	N/A	ENSP00000451648.1	Q9Y4C0-3
	NRXN3	ENST00000428277.6	TSL:1	c.248-49739T>C		intron	N/A	ENSP00000394426.2	Q9HDB5-4

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47884 AN: 151782 Hom.: 8216 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.315 AC: 47903 AN: 151902 Hom.: 8221 Cov.: 32 AF XY: 0.315 AC XY: 23391 AN XY: 74216

African (AFR) AF: 0.190 AC: 7894 AN: 41450

American (AMR) AF: 0.331 AC: 5039 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1937 AN: 3466

East Asian (EAS) AF: 0.206 AC: 1059 AN: 5142

South Asian (SAS) AF: 0.374 AC: 1800 AN: 4814

European-Finnish (FIN) AF: 0.340 AC: 3589 AN: 10552

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25409 AN: 67924

Other (OTH) AF: 0.360 AC: 759 AN: 2108

Alfa AF: 0.327 Hom.: 1219

Bravo AF: 0.308

Asia WGS AF: 0.279 AC: 969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.039
DANN	Benign	0.54
PhyloP100		-2.6
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: rs2217887; hg19: chr14-79883825;