14-79045057-T-C

Variant names:

• chr14-79045057-T-C
• rs2062743
• NM_001330195.2:c.3262+56916T>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+56916T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,252 control chromosomes in the GnomAD database, including 67,815 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 0.94 (67815 hom., cov: 31)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798
• Publications: 1 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3262+56916T>C		intron_variant	Intron 15 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.3262+56916T>C		intron_variant	Intron 15 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143111 AN: 152134 Hom.: 67780 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.982

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.961

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

GnomAD4 genome AF: 0.941 AC: 143201 AN: 152252 Hom.: 67815 Cov.: 31 AF XY: 0.942 AC XY: 70144 AN XY: 74440

African (AFR) AF: 0.823 AC: 34167 AN: 41514

American (AMR) AF: 0.982 AC: 15029 AN: 15302

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3469 AN: 3470

East Asian (EAS) AF: 0.940 AC: 4869 AN: 5180

South Asian (SAS) AF: 0.982 AC: 4729 AN: 4816

European-Finnish (FIN) AF: 0.967 AC: 10257 AN: 10608

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.991 AC: 67464 AN: 68046

Other (OTH) AF: 0.955 AC: 2016 AN: 2110

Alfa AF: 0.959 Hom.: 9227

Bravo AF: 0.936

Asia WGS AF: 0.941 AC: 3272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.0
DANN	Benign	0.80
PhyloP100		0.80
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: rs2062743; hg19: chr14-79511400;