rs31393

Variant names:

• chr14-78890272-A-G
• rs31393
• NM_001330195.2:c.2276-66970A>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.2276-66970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,950 control chromosomes in the GnomAD database, including 3,000 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 0.14 (3000 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.2276-66970A>G		intron_variant	Intron 10 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.2276-66970A>G		intron_variant	Intron 10 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20887 AN: 151832 Hom.: 2996 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0704

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.138 AC: 20926 AN: 151950 Hom.: 3000 Cov.: 32 AF XY: 0.134 AC XY: 9963 AN XY: 74272

African (AFR) AF: 0.367 AC: 15188 AN: 41414

American (AMR) AF: 0.0701 AC: 1068 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0930 AC: 322 AN: 3462

East Asian (EAS) AF: 0.127 AC: 655 AN: 5146

South Asian (SAS) AF: 0.145 AC: 700 AN: 4818

European-Finnish (FIN) AF: 0.0159 AC: 169 AN: 10614

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0364 AC: 2471 AN: 67946

Other (OTH) AF: 0.125 AC: 264 AN: 2114

Alfa AF: 0.0802 Hom.: 634

Bravo AF: 0.152

Asia WGS AF: 0.148 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.41
PhyloP100		-0.54
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: rs31393; hg19: chr14-79356615;