rs221424

Variant names:

• chr14-79592678-A-G
• rs221424
• NM_001330195.2:c.3445-71100A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-79592678-A-G
• chr14-79592678-A-T

Variant summary

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

The NM_001330195.2(NRXN3):​c.3445-71100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,160 control chromosomes in the GnomAD database, including 1,948 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 0.12 (1948 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3445-71100A>G		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.3445-71100A>G		intron_variant	Intron 16 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18300 AN: 152040 Hom.: 1949 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.0790

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.120 AC: 18310 AN: 152160 Hom.: 1948 Cov.: 32 AF XY: 0.117 AC XY: 8712 AN XY: 74394

African (AFR) AF: 0.280 AC: 11592 AN: 41452

American (AMR) AF: 0.0631 AC: 965 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.181 AC: 939 AN: 5180

South Asian (SAS) AF: 0.0785 AC: 378 AN: 4816

European-Finnish (FIN) AF: 0.0240 AC: 255 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0531 AC: 3615 AN: 68018

Other (OTH) AF: 0.100 AC: 212 AN: 2110

Alfa AF: 0.0836 Hom.: 213

Bravo AF: 0.132

Asia WGS AF: 0.120 AC: 417 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.75
PhyloP100		1.2
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: rs221424; hg19: chr14-80059021;