chr14-33599495-A-G

Variant names:

• chr14-33599495-A-G
• rs8004379
• NM_001164749.2:c.558+39285A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164749.2(NPAS3):​c.558+39285A>G variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.29
• Publications: 6 publications found

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]

ENSG00000287153 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164749.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS3	NM_001164749.2	MANE Select	c.558+39285A>G		intron	N/A	NP_001158221.1
	NPAS3	NM_173159.3		c.519+39285A>G		intron	N/A	NP_775182.1
	NPAS3	NM_001394988.1		c.513+39285A>G		intron	N/A	NP_001381917.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS3	ENST00000356141.9	TSL:1 MANE Select	c.558+39285A>G		intron	N/A	ENSP00000348460.4
	NPAS3	ENST00000357798.9	TSL:1	c.519+39285A>G		intron	N/A	ENSP00000350446.5
	NPAS3	ENST00000548645.5	TSL:1	c.468+39285A>G		intron	N/A	ENSP00000448916.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Benign	0.88
PhyloP100		6.3

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

Other links and lift over

dbSNP: rs8004379; hg19: chr14-34068701;