14-33214911-C-T

Position:

• chr14-33214911-C-T

Variant summary

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

The ENST00000547068.5(NPAS3):​c.-437C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 440,672 control chromosomes in the GnomAD database, including 152,328 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 0.78 (47511 hom., cov: 32)
  • Exomes 𝑓: 0.85 (104817 hom.)
• Consequence: NPAS3 ENST00000547068.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS3	NM_001164749.2	c.141-271C>T		intron_variant		ENST00000356141.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS3	ENST00000356141.9	c.141-271C>T		intron_variant		1	NM_001164749.2	A2

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118700 AN: 151918 Hom.: 47470 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.813

GnomAD4 exome AF: 0.850 AC: 245401 AN: 288636 Hom.: 104817 Cov.: 3 AF XY: 0.854 AC XY: 130380 AN XY: 152728

Gnomad4 AFR exome AF: 0.591

Gnomad4 AMR exome AF: 0.902

Gnomad4 ASJ exome AF: 0.899

Gnomad4 EAS exome AF: 0.822

Gnomad4 SAS exome AF: 0.877

Gnomad4 FIN exome AF: 0.828

Gnomad4 NFE exome AF: 0.857

Gnomad4 OTH exome AF: 0.848

GnomAD4 genome AF: 0.781 AC: 118791 AN: 152036 Hom.: 47511 Cov.: 32 AF XY: 0.783 AC XY: 58157 AN XY: 74310

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.864

Gnomad4 ASJ AF: 0.899

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.856

Gnomad4 OTH AF: 0.811

Alfa AF: 0.775 Hom.: 2853

Bravo AF: 0.778

Asia WGS AF: 0.846 AC: 2941 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.2
DANN	Benign	0.52

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: rs7151302; hg19: chr14-33684117;