14-78552002-A-C

Variant names:

• chr14-78552002-A-C
• rs918270
• NM_001330195.2:c.758-93118A>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.758-93118A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,006 control chromosomes in the GnomAD database, including 4,527 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 0.24 (4527 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330195.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	NM_001330195.2	MANE Select	c.758-93118A>C		intron	N/A	NP_001317124.1	A0A0A0MR89
	NRXN3	NM_001366425.1		c.758-93118A>C		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.770-93118A>C		intron	N/A	NP_001353355.1	A0A0U1RQC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.758-93118A>C		intron	N/A	ENSP00000338349.7	A0A0A0MR89
	NRXN3	ENST00000554719.5	TSL:1	c.-362-93118A>C		intron	N/A	ENSP00000451648.1	Q9Y4C0-3
	NRXN3	ENST00000634499.2	TSL:5	c.770-93118A>C		intron	N/A	ENSP00000488920.2	A0A0U1RQC5

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35888 AN: 151888 Hom.: 4530 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.236 AC: 35898 AN: 152006 Hom.: 4527 Cov.: 32 AF XY: 0.236 AC XY: 17550 AN XY: 74260

African (AFR) AF: 0.173 AC: 7166 AN: 41466

American (AMR) AF: 0.180 AC: 2751 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 888 AN: 3468

East Asian (EAS) AF: 0.207 AC: 1066 AN: 5154

South Asian (SAS) AF: 0.256 AC: 1229 AN: 4808

European-Finnish (FIN) AF: 0.268 AC: 2828 AN: 10542

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.281 AC: 19118 AN: 67978

Other (OTH) AF: 0.243 AC: 511 AN: 2106

Alfa AF: 0.264 Hom.: 23638

Bravo AF: 0.225

Asia WGS AF: 0.244 AC: 848 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	14
DANN	Benign	0.48
PhyloP100		0.36
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: rs918270; hg19: chr14-79018345;