rs17406989

Variant names:

• chr14-33614444-C-A
• rs17406989
• NM_001164749.2:c.558+54234C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-33614444-C-A
• chr14-33614444-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164749.2(NPAS3):​c.558+54234C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0995 in 152,176 control chromosomes in the GnomAD database, including 840 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 0.10 (840 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

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+54234C>A		intron	N/A	NP_001158221.1
	NPAS3	NM_173159.3		c.519+54234C>A		intron	N/A	NP_775182.1
	NPAS3	NM_001394988.1		c.513+54234C>A		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+54234C>A		intron	N/A	ENSP00000348460.4
	NPAS3	ENST00000357798.9	TSL:1	c.519+54234C>A		intron	N/A	ENSP00000350446.5
	NPAS3	ENST00000548645.5	TSL:1	c.468+54234C>A		intron	N/A	ENSP00000448916.1

Frequencies

GnomAD3 genomes AF: 0.0995 AC: 15128 AN: 152058 Hom.: 836 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0673

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0293

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0371

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0900

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0995 AC: 15144 AN: 152176 Hom.: 840 Cov.: 32 AF XY: 0.0975 AC XY: 7254 AN XY: 74408

African (AFR) AF: 0.143 AC: 5938 AN: 41508

American (AMR) AF: 0.0672 AC: 1027 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3468

East Asian (EAS) AF: 0.0291 AC: 151 AN: 5182

South Asian (SAS) AF: 0.165 AC: 796 AN: 4812

European-Finnish (FIN) AF: 0.0371 AC: 394 AN: 10612

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0900 AC: 6117 AN: 67988

Other (OTH) AF: 0.0990 AC: 209 AN: 2112

Alfa AF: 0.0923 Hom.: 1517

Bravo AF: 0.102

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		0.096
Mutation Taster		=100/0	polymorphism (auto)

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: rs17406989; hg19: chr14-34083650;