Variant chr14-33799807-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001164749.2(NPAS3):c.1500G>C(p.Arg500=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,613,604 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 6 hom. )

Consequence

NPAS3
NM_001164749.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.348

Variant links:

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]

NPAS3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 14-33799807-G-C is Benign according to our data. Variant chr14-33799807-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2644159.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.348 with no splicing effect.

BS2

High AC in GnomAd4 at 242 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS3	NM_001164749.2 linkuse as main transcript	c.1500G>C	p.Arg500=	synonymous_variant	12/12	ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9 linkuse as main transcript	c.1500G>C	p.Arg500=	synonymous_variant	12/12	1	NM_001164749.2	ENSP00000348460	A2	Q8IXF0-1

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

242

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00259

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00163

AC:

404

AN:

248356

Hom.:

AF XY:

0.00172

AC XY:

231

AN XY:

134692

show subpopulations

Gnomad AFR exome

AF:

0.000441

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00410

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00180

Gnomad FIN exome

AF:

0.000994

Gnomad NFE exome

AF:

0.00233

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00245

AC:

3577

AN:

1461298

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

1731

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00371

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00213

Gnomad4 FIN exome

AF:

0.00148

Gnomad4 NFE exome

AF:

0.00272

Gnomad4 OTH exome

AF:

0.00268

GnomAD4 genome

AF:

0.00159

AC:

242

AN:

152306

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00259

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00154

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00268

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

NPAS3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over