NM_001330195.2:c.291C>T

Variant names:

• chr14-78243384-C-T
• rs138817150
• NM_001330195.2:c.291C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001330195.2(NRXN3):​c.291C>T​(p.Ala97Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000991 in 1,565,370 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00096 (6 hom.)
• Consequence: NRXN3 NM_001330195.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -4.78

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-78243384-C-T is Benign according to our data. Variant chr14-78243384-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3045674.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-4.78 with no splicing effect.
• BS2: High AC in GnomAd4 at 194 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.291C>T	p.Ala97Ala	synonymous_variant	Exon 2 of 21	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.291C>T	p.Ala97Ala	synonymous_variant	Exon 2 of 21	5	NM_001330195.2	ENSP00000338349.7
NRXN3	ENST00000634499.2	c.291C>T	p.Ala97Ala	synonymous_variant	Exon 2 of 22	5		ENSP00000488920.2
NRXN3	ENST00000554738.5	c.291C>T	p.Ala97Ala	synonymous_variant	Exon 1 of 20	5		ENSP00000450683.1

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 194 AN: 152242 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00234

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00105 AC: 187 AN: 178520 Hom.: 0 AF XY: 0.000969 AC XY: 95 AN XY: 98000

Gnomad AFR exome AF: 0.000207

Gnomad AMR exome AF: 0.000140

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00262

Gnomad NFE exome AF: 0.00188

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.000961 AC: 1358 AN: 1413010 Hom.: 6 Cov.: 30 AF XY: 0.00105 AC XY: 732 AN XY: 700106

Gnomad4 AFR exome AF: 0.000367

Gnomad4 AMR exome AF: 0.000176

Gnomad4 ASJ exome AF: 0.000118

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000123

Gnomad4 FIN exome AF: 0.00322

Gnomad4 NFE exome AF: 0.00104

Gnomad4 OTH exome AF: 0.00130

GnomAD4 genome AF: 0.00127 AC: 194 AN: 152360 Hom.: 1 Cov.: 32 AF XY: 0.00132 AC XY: 98 AN XY: 74510

Gnomad4 AFR AF: 0.000240

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.00234

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00445 Hom.: 1

Bravo AF: 0.000827

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NRXN3-related disorder Benign:1

Oct 24, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.39
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs138817150; hg19: chr14-78709727;