NM_001330195.2:c.51G>A

Variant names:

• chr14-78243144-G-A
• rs1034245105
• NM_001330195.2:c.51G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_001330195.2(NRXN3):​c.51G>A​(p.Leu17Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,546,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: NRXN3 NM_001330195.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.42
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 14-78243144-G-A is Benign according to our data. Variant chr14-78243144-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3047705.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.42 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 37 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	NM_001330195.2	MANE Select	c.51G>A	p.Leu17Leu	synonymous	Exon 2 of 21	NP_001317124.1	A0A0A0MR89
	NRXN3	NM_001366425.1		c.51G>A	p.Leu17Leu	synonymous	Exon 2 of 20	NP_001353354.1
	NRXN3	NM_001366426.1		c.51G>A	p.Leu17Leu	synonymous	Exon 2 of 22	NP_001353355.1	A0A0U1RQC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.51G>A	p.Leu17Leu	synonymous	Exon 2 of 21	ENSP00000338349.7	A0A0A0MR89
	NRXN3	ENST00000634499.2	TSL:5	c.51G>A	p.Leu17Leu	synonymous	Exon 2 of 22	ENSP00000488920.2	A0A0U1RQC5
	NRXN3	ENST00000554738.5	TSL:5	c.51G>A	p.Leu17Leu	synonymous	Exon 1 of 20	ENSP00000450683.1	Q9Y4C0-4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000198 AC: 3 AN: 151730 AF XY: 0.0000242

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000475

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000265 AC: 37 AN: 1393876 Hom.: 0 Cov.: 30 AF XY: 0.0000363 AC XY: 25 AN XY: 688744

African (AFR) AF: 0.00 AC: 0 AN: 31954

American (AMR) AF: 0.00 AC: 0 AN: 37234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25266

East Asian (EAS) AF: 0.00 AC: 0 AN: 36428

South Asian (SAS) AF: 0.00 AC: 0 AN: 79510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.0000313 AC: 34 AN: 1084868

Other (OTH) AF: 0.0000514 AC: 3 AN: 58388

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74376

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NRXN3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.1
DANN	Benign	0.73
PhyloP100		2.4

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: rs1034245105; hg19: chr14-78709487;