NM_001330195.2:c.4014+9955C>A

Variant names:

• chr14-79707892-C-A
• rs1861957
• NM_001330195.2:c.4014+9955C>A

Variant summary

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

The NM_001330195.2(NRXN3):​c.4014+9955C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,948 control chromosomes in the GnomAD database, including 17,990 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 0.48 (17990 hom., cov: 33)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• 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

ENSG00000258637 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.599 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.4014+9955C>A		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.3924+9955C>A		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.4026+9955C>A		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.4014+9955C>A		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.2805+9955C>A		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000428277.6	TSL:1	c.999+9955C>A		intron	N/A	ENSP00000394426.2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72672 AN: 151830 Hom.: 17972 Cov.: 33

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.479 AC: 72728 AN: 151948 Hom.: 17990 Cov.: 33 AF XY: 0.476 AC XY: 35312 AN XY: 74256

African (AFR) AF: 0.605 AC: 25078 AN: 41444

American (AMR) AF: 0.388 AC: 5920 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3472

East Asian (EAS) AF: 0.371 AC: 1915 AN: 5168

South Asian (SAS) AF: 0.555 AC: 2673 AN: 4820

European-Finnish (FIN) AF: 0.335 AC: 3529 AN: 10538

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30543 AN: 67930

Other (OTH) AF: 0.442 AC: 932 AN: 2108

Alfa AF: 0.454 Hom.: 23959

Bravo AF: 0.484

Asia WGS AF: 0.453 AC: 1571 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.5
DANN	Benign	0.32
PhyloP100		0.19
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: rs1861957; hg19: chr14-80174235;