14-33139900-T-C

Variant names:

• chr14-33139900-T-C
• rs10137682
• NM_001164749.2:c.141-75282T>C

Variant summary

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

The NM_001164749.2(NPAS3):​c.141-75282T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,624 control chromosomes in the GnomAD database, including 15,599 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 0.44 (15599 hom., cov: 30)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 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.141-75282T>C		intron	N/A	NP_001158221.1
	NPAS3	NM_173159.3		c.51-75282T>C		intron	N/A	NP_775182.1
	NPAS3	NM_001394988.1		c.51-75282T>C		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.141-75282T>C		intron	N/A	ENSP00000348460.4
	NPAS3	ENST00000357798.9	TSL:1	c.51-75282T>C		intron	N/A	ENSP00000350446.5
	NPAS3	ENST00000548645.5	TSL:1	c.51-75282T>C		intron	N/A	ENSP00000448916.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66565 AN: 151512 Hom.: 15577 Cov.: 30

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.440 AC: 66642 AN: 151624 Hom.: 15599 Cov.: 30 AF XY: 0.437 AC XY: 32352 AN XY: 74074

African (AFR) AF: 0.604 AC: 24968 AN: 41332

American (AMR) AF: 0.441 AC: 6705 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1541 AN: 3464

East Asian (EAS) AF: 0.260 AC: 1335 AN: 5142

South Asian (SAS) AF: 0.388 AC: 1860 AN: 4798

European-Finnish (FIN) AF: 0.369 AC: 3859 AN: 10446

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25123 AN: 67912

Other (OTH) AF: 0.428 AC: 902 AN: 2106

Alfa AF: 0.428 Hom.: 2909

Bravo AF: 0.455

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.65
PhyloP100		-0.31
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: rs10137682; hg19: chr14-33609106;