rs12433161

Positions:

• chr14-33196383-C-T

Variant summary

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

The NM_001164749.2(NPAS3):​c.141-18799C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,144 control chromosomes in the GnomAD database, including 3,839 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 0.21 (3839 hom., cov: 33)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS3	NM_001164749.2	c.141-18799C>T		intron_variant		ENST00000356141.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS3	ENST00000356141.9	c.141-18799C>T		intron_variant		1	NM_001164749.2	A2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32110 AN: 152026 Hom.: 3839 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.211 AC: 32112 AN: 152144 Hom.: 3839 Cov.: 33 AF XY: 0.221 AC XY: 16397 AN XY: 74362

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.230

Alfa AF: 0.213 Hom.: 718

Bravo AF: 0.211

Asia WGS AF: 0.304 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.9
DANN	Benign	0.49

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: rs12433161; hg19: chr14-33665589;