14-79474040-G-T

Variant names:

• chr14-79474040-G-T
• rs7144011
• NM_001330195.2:c.3444+6638G>T

Variant summary

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

The NM_001330195.2(NRXN3):​c.3444+6638G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,052 control chromosomes in the GnomAD database, including 3,411 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 0.21 (3411 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 34 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 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.3444+6638G>T		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.3444+6638G>T		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.3456+6638G>T		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.3444+6638G>T		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.2325+6638G>T		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000428277.6	TSL:1	c.429+6638G>T		intron	N/A	ENSP00000394426.2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31534 AN: 151934 Hom.: 3409 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.207 AC: 31541 AN: 152052 Hom.: 3411 Cov.: 32 AF XY: 0.205 AC XY: 15254 AN XY: 74332

African (AFR) AF: 0.231 AC: 9590 AN: 41482

American (AMR) AF: 0.207 AC: 3166 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 411 AN: 3470

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5168

South Asian (SAS) AF: 0.112 AC: 542 AN: 4818

European-Finnish (FIN) AF: 0.233 AC: 2469 AN: 10576

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14829 AN: 67950

Other (OTH) AF: 0.181 AC: 381 AN: 2110

Alfa AF: 0.219 Hom.: 741

Bravo AF: 0.207

Asia WGS AF: 0.0650 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.5
DANN	Benign	0.66
PhyloP100		1.1
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: rs7144011; hg19: chr14-79940383;