chr14-78921999-C-T

Variant names:

• chr14-78921999-C-T
• rs17757879
• NM_001330195.2:c.2276-35243C>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.2276-35243C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,166 control chromosomes in the GnomAD database, including 1,231 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 (1231 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.2276-35243C>T		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.2276-35243C>T		intron_variant	Intron 10 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16513 AN: 152048 Hom.: 1231 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0900

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0497

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.109 AC: 16513 AN: 152166 Hom.: 1231 Cov.: 32 AF XY: 0.109 AC XY: 8134 AN XY: 74366

African (AFR) AF: 0.0269 AC: 1118 AN: 41542

American (AMR) AF: 0.125 AC: 1902 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0900 AC: 312 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.0500 AC: 241 AN: 4824

European-Finnish (FIN) AF: 0.188 AC: 1982 AN: 10564

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10632 AN: 67994

Other (OTH) AF: 0.122 AC: 257 AN: 2108

Alfa AF: 0.131 Hom.: 259

Bravo AF: 0.0989

Asia WGS AF: 0.0250 AC: 87 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.72
PhyloP100		0.14
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: rs17757879; hg19: chr14-79388342;