NM_001330195.2:c.757+21874A>C

Variant names:

• chr14-78319734-A-C
• rs11624704
• NM_001330195.2:c.757+21874A>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.757+21874A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,020 control chromosomes in the GnomAD database, including 1,272 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 0.13 (1272 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.714
• Publications: 33 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 (SAS) allele frequency at 95% confidence interval = 0.151 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.757+21874A>C		intron	N/A	NP_001317124.1	A0A0A0MR89
	NRXN3	NM_001366425.1		c.757+21874A>C		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.769+19043A>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.757+21874A>C		intron	N/A	ENSP00000338349.7	A0A0A0MR89
	NRXN3	ENST00000634499.2	TSL:5	c.769+19043A>C		intron	N/A	ENSP00000488920.2	A0A0U1RQC5
	NRXN3	ENST00000554738.5	TSL:5	c.751+19043A>C		intron	N/A	ENSP00000450683.1	Q9Y4C0-4

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19275 AN: 151902 Hom.: 1271 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0701

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.127 AC: 19284 AN: 152020 Hom.: 1272 Cov.: 32 AF XY: 0.126 AC XY: 9378 AN XY: 74322

African (AFR) AF: 0.114 AC: 4727 AN: 41438

American (AMR) AF: 0.126 AC: 1925 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3470

East Asian (EAS) AF: 0.0701 AC: 362 AN: 5164

South Asian (SAS) AF: 0.160 AC: 772 AN: 4812

European-Finnish (FIN) AF: 0.112 AC: 1184 AN: 10568

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9303 AN: 67972

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.137 Hom.: 6589

Bravo AF: 0.126

Asia WGS AF: 0.115 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.50
PhyloP100		0.71

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: rs11624704; hg19: chr14-78786077;