rs7147705

Variant names:

• chr14-79535753-T-C
• rs7147705
• NM_001330195.2:c.3444+68351T>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.3444+68351T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,992 control chromosomes in the GnomAD database, including 27,660 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 0.57 (27660 hom., cov: 31)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609
• Publications: 9 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3444+68351T>C		intron_variant	Intron 16 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.3444+68351T>C		intron_variant	Intron 16 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86164 AN: 151874 Hom.: 27655 Cov.: 31

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.567 AC: 86182 AN: 151992 Hom.: 27660 Cov.: 31 AF XY: 0.569 AC XY: 42281 AN XY: 74272

African (AFR) AF: 0.254 AC: 10530 AN: 41468

American (AMR) AF: 0.689 AC: 10518 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1760 AN: 3470

East Asian (EAS) AF: 0.567 AC: 2915 AN: 5142

South Asian (SAS) AF: 0.488 AC: 2349 AN: 4810

European-Finnish (FIN) AF: 0.725 AC: 7656 AN: 10556

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48543 AN: 67954

Other (OTH) AF: 0.539 AC: 1138 AN: 2112

Alfa AF: 0.651 Hom.: 74435

Bravo AF: 0.554

Asia WGS AF: 0.475 AC: 1653 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	0.78
DANN	Benign	0.74
PhyloP100		-0.61
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: rs7147705; hg19: chr14-80002096;