rs10483437

Variant names:

• chr14-33366595-T-A
• rs10483437
• NM_001164749.2:c.386-591T>A

Variant summary

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

The ENST00000356141.9(NPAS3):​c.386-591T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,078 control chromosomes in the GnomAD database, including 6,180 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 0.27 (6180 hom., cov: 32)
• Consequence: NPAS3 ENST00000356141.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000356141.9. 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.386-591T>A		intron	N/A	NP_001158221.1
	NPAS3	NM_173159.3		c.347-591T>A		intron	N/A	NP_775182.1
	NPAS3	NM_001394988.1		c.347-597T>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.386-591T>A		intron	N/A	ENSP00000348460.4
	NPAS3	ENST00000357798.9	TSL:1	c.347-591T>A		intron	N/A	ENSP00000350446.5
	NPAS3	ENST00000548645.5	TSL:1	c.296-591T>A		intron	N/A	ENSP00000448916.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41716 AN: 151960 Hom.: 6168 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.275 AC: 41760 AN: 152078 Hom.: 6180 Cov.: 32 AF XY: 0.269 AC XY: 20020 AN XY: 74348

African (AFR) AF: 0.340 AC: 14105 AN: 41454

American (AMR) AF: 0.230 AC: 3507 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3472

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5184

South Asian (SAS) AF: 0.150 AC: 721 AN: 4820

European-Finnish (FIN) AF: 0.221 AC: 2340 AN: 10584

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19545 AN: 67988

Other (OTH) AF: 0.250 AC: 529 AN: 2114

Alfa AF: 0.282 Hom.: 759

Bravo AF: 0.276

Asia WGS AF: 0.0840 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.42
PhyloP100		-1.1
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: rs10483437; hg19: chr14-33835801;