NM_001330195.2:c.758-100119A>G

Variant names:

• chr14-78545001-A-G
• rs10144398
• NM_001330195.2:c.758-100119A>G

Variant summary

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

The NM_001330195.2(NRXN3):​c.758-100119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,066 control chromosomes in the GnomAD database, including 34,025 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 0.67 (34025 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	NM_001330195.2	MANE Select	c.758-100119A>G		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.758-100119A>G		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.770-100119A>G		intron	N/A	NP_001353355.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.758-100119A>G		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.-362-100119A>G		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000634499.2	TSL:5	c.770-100119A>G		intron	N/A	ENSP00000488920.2

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101151 AN: 151948 Hom.: 34007 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.666 AC: 101216 AN: 152066 Hom.: 34025 Cov.: 32 AF XY: 0.668 AC XY: 49658 AN XY: 74340

African (AFR) AF: 0.582 AC: 24123 AN: 41450

American (AMR) AF: 0.615 AC: 9398 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2110 AN: 3470

East Asian (EAS) AF: 0.685 AC: 3540 AN: 5168

South Asian (SAS) AF: 0.673 AC: 3238 AN: 4812

European-Finnish (FIN) AF: 0.807 AC: 8542 AN: 10588

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48119 AN: 67984

Other (OTH) AF: 0.627 AC: 1324 AN: 2112

Alfa AF: 0.679 Hom.: 4927

Bravo AF: 0.643

Asia WGS AF: 0.669 AC: 2328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.4
DANN	Benign	0.66
PhyloP100		0.46
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: rs10144398; hg19: chr14-79011344;