14-79132931-T-C

Variant names:

• chr14-79132931-T-C
• rs6574495
• NM_001330195.2:c.3262+144790T>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.3262+144790T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,030 control chromosomes in the GnomAD database, including 23,086 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 0.53 (23086 hom., cov: 33)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 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.3262+144790T>C		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.3262+144790T>C		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.3274+144790T>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.3262+144790T>C		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.2143+144790T>C		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000634499.2	TSL:5	c.3274+144790T>C		intron	N/A	ENSP00000488920.2

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80653 AN: 151912 Hom.: 23087 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.531 AC: 80678 AN: 152030 Hom.: 23086 Cov.: 33 AF XY: 0.540 AC XY: 40140 AN XY: 74304

African (AFR) AF: 0.326 AC: 13518 AN: 41428

American (AMR) AF: 0.445 AC: 6802 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1814 AN: 3468

East Asian (EAS) AF: 0.773 AC: 3978 AN: 5146

South Asian (SAS) AF: 0.637 AC: 3068 AN: 4820

European-Finnish (FIN) AF: 0.769 AC: 8146 AN: 10596

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41478 AN: 67978

Other (OTH) AF: 0.533 AC: 1127 AN: 2116

Alfa AF: 0.585 Hom.: 112942

Bravo AF: 0.494

Asia WGS AF: 0.654 AC: 2276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.37
PhyloP100		-0.21
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: rs6574495; hg19: chr14-79599274;