rs7157669

Variant names:

• chr14-78471334-C-A
• rs7157669
• NM_001330195.2:c.757+173474C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-78471334-C-A
• chr14-78471334-C-G
• chr14-78471334-C-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.757+173474C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.093 (7 hom., cov: 0)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.757+173474C>A		intron_variant	Intron 4 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.757+173474C>A		intron_variant	Intron 4 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 961 AN: 10332 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0737

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0929 AC: 960 AN: 10330 Hom.: 7 Cov.: 0 AF XY: 0.0877 AC XY: 448 AN XY: 5110

African (AFR) AF: 0.0895 AC: 344 AN: 3844

American (AMR) AF: 0.0740 AC: 92 AN: 1244

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 59 AN: 316

East Asian (EAS) AF: 0.0155 AC: 10 AN: 644

South Asian (SAS) AF: 0.133 AC: 22 AN: 166

European-Finnish (FIN) AF: 0.0384 AC: 29 AN: 756

Middle Eastern (MID) AF: 0.115 AC: 3 AN: 26

European-Non Finnish (NFE) AF: 0.121 AC: 383 AN: 3174

Other (OTH) AF: 0.113 AC: 16 AN: 142

Alfa AF: 0.851 Hom.: 72606

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.22
DANN	Benign	0.33
PhyloP100		-2.1
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: rs7157669; hg19: chr14-78937677; COSMIC: COSV73577932;