rs10137682

Positions:

• chr14-33139900-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164749.2(NPAS3):​c.141-75282T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,624 control chromosomes in the GnomAD database, including 15,599 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 0.44 (15599 hom., cov: 30)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

Genes affected

NPAS3 (HGNC:19311): (neuronal PAS domain protein 3) This gene encodes a member of the basic helix-loop-helix and PAS domain-containing family of transcription factors. The encoded protein is localized to the nucleus and may regulate genes involved in neurogenesis. Chromosomal abnormalities that affect the coding potential of this gene are associated with schizophrenia and cognitive disability. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS3	NM_001164749.2	c.141-75282T>C		intron_variant		ENST00000356141.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS3	ENST00000356141.9	c.141-75282T>C		intron_variant		1	NM_001164749.2	A2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66565 AN: 151512 Hom.: 15577 Cov.: 30

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.440 AC: 66642 AN: 151624 Hom.: 15599 Cov.: 30 AF XY: 0.437 AC XY: 32352 AN XY: 74074

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.428

Alfa AF: 0.424 Hom.: 2783

Bravo AF: 0.455

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.65

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: rs10137682; hg19: chr14-33609106;