rs10483422

chr14-33009299-A-G

Variant summary

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

The NM_001164749.2(NPAS3):c.51-46606A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 152,226 control chromosomes in the GnomAD database, including 921 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 0.088 (921 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS3	NM_001164749.2	c.51-46606A>G		intron_variant		ENST00000356141.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS3	ENST00000356141.9	c.51-46606A>G		intron_variant		1	NM_001164749.2	A2

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13386 AN: 152108 Hom.: 920 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0985

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0888

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0320

Gnomad OTH AF: 0.0736

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

GnomAD4 genome AF: 0.0880 AC: 13400 AN: 152226 Hom.: 921 Cov.: 32 AF XY: 0.0884 AC XY: 6581 AN XY: 74438

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0985

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.0996

Gnomad4 FIN AF: 0.0888

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0485 Hom.: 386

Bravo AF: 0.0940

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.9
Dann	Benign	0.48

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: rs10483422; hg19: chr14-33478505;