14-78759493-T-C

Variant names:

• chr14-78759493-T-C
• rs7154021
• NM_001330195.2:c.2045-44127T>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.2045-44127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,152 control chromosomes in the GnomAD database, including 3,930 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 0.17 (3930 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• 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 (AFR) allele frequency at 95% confidence interval = 0.403 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.2045-44127T>C		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.2045-44127T>C		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.2057-44127T>C		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.2045-44127T>C		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.926-44127T>C		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000556496.2	TSL:1	n.1389-44127T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25808 AN: 152034 Hom.: 3928 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0358

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0735

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.170 AC: 25836 AN: 152152 Hom.: 3930 Cov.: 32 AF XY: 0.167 AC XY: 12399 AN XY: 74394

African (AFR) AF: 0.408 AC: 16924 AN: 41446

American (AMR) AF: 0.0953 AC: 1457 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3472

East Asian (EAS) AF: 0.0355 AC: 184 AN: 5188

South Asian (SAS) AF: 0.163 AC: 787 AN: 4820

European-Finnish (FIN) AF: 0.0548 AC: 581 AN: 10610

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0735 AC: 4996 AN: 68002

Other (OTH) AF: 0.153 AC: 323 AN: 2116

Alfa AF: 0.108 Hom.: 4948

Bravo AF: 0.181

Asia WGS AF: 0.123 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0080
DANN	Benign	0.44
PhyloP100		-2.0
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: rs7154021; hg19: chr14-79225836;