NM_001330195.2:c.3707-1534T>C

Variant names:

• chr14-79696096-T-C
• rs12147956
• NM_001330195.2:c.3707-1534T>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.3707-1534T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 151,920 control chromosomes in the GnomAD database, including 876 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 0.11 (876 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3707-1534T>C		intron_variant	Intron 18 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.3707-1534T>C		intron_variant	Intron 18 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15934 AN: 151800 Hom.: 870 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0705

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0966

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.105 AC: 15959 AN: 151920 Hom.: 876 Cov.: 32 AF XY: 0.104 AC XY: 7726 AN XY: 74252

African (AFR) AF: 0.131 AC: 5431 AN: 41462

American (AMR) AF: 0.0737 AC: 1123 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 508 AN: 3466

East Asian (EAS) AF: 0.133 AC: 683 AN: 5138

South Asian (SAS) AF: 0.124 AC: 596 AN: 4822

European-Finnish (FIN) AF: 0.0705 AC: 747 AN: 10602

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0966 AC: 6556 AN: 67872

Other (OTH) AF: 0.104 AC: 219 AN: 2110

Alfa AF: 0.0992 Hom.: 935

Bravo AF: 0.107

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.65
PhyloP100		-0.071
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: rs12147956; hg19: chr14-80162439;