14-78396376-A-G

Variant names:

• chr14-78396376-A-G
• rs2192420
• NM_001330195.2:c.757+98516A>G

Variant summary

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

The NM_001330195.2(NRXN3):​c.757+98516A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,190 control chromosomes in the GnomAD database, including 59,083 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 0.88 (59083 hom., cov: 33)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.932 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.757+98516A>G		intron	N/A	NP_001317124.1	A0A0A0MR89
	NRXN3	NM_001366425.1		c.757+98516A>G		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.769+95685A>G		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.757+98516A>G		intron	N/A	ENSP00000338349.7	A0A0A0MR89
	NRXN3	ENST00000634499.2	TSL:5	c.769+95685A>G		intron	N/A	ENSP00000488920.2	A0A0U1RQC5
	NRXN3	ENST00000554738.5	TSL:5	c.751+95685A>G		intron	N/A	ENSP00000450683.1	Q9Y4C0-4

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133340 AN: 152072 Hom.: 59046 Cov.: 33

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.897

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

GnomAD4 genome AF: 0.877 AC: 133421 AN: 152190 Hom.: 59083 Cov.: 33 AF XY: 0.879 AC XY: 65415 AN XY: 74410

African (AFR) AF: 0.750 AC: 31142 AN: 41508

American (AMR) AF: 0.939 AC: 14352 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 3331 AN: 3470

East Asian (EAS) AF: 0.690 AC: 3569 AN: 5172

South Asian (SAS) AF: 0.946 AC: 4558 AN: 4820

European-Finnish (FIN) AF: 0.912 AC: 9667 AN: 10598

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63773 AN: 68008

Other (OTH) AF: 0.898 AC: 1901 AN: 2116

Alfa AF: 0.897 Hom.: 48945

Bravo AF: 0.872

Asia WGS AF: 0.828 AC: 2877 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.8
DANN	Benign	0.47
PhyloP100		0.48

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: rs2192420; hg19: chr14-78862719;