14-33800569-C-T

Variant names:

• chr14-33800569-C-T
• rs10142034
• NM_001164749.2:c.2262C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001164749.2(NPAS3):​c.2262C>T​(p.Ser754Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPAS3 NM_001164749.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 8 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=1.61 with no splicing effect.

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.2262C>T	p.Ser754Ser	synonymous	Exon 12 of 12	NP_001158221.1
	NPAS3	NM_173159.3		c.2223C>T	p.Ser741Ser	synonymous	Exon 12 of 12	NP_775182.1
	NPAS3	NM_001394988.1		c.2217C>T	p.Ser739Ser	synonymous	Exon 12 of 12	NP_001381917.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS3	ENST00000356141.9	TSL:1 MANE Select	c.2262C>T	p.Ser754Ser	synonymous	Exon 12 of 12	ENSP00000348460.4
	NPAS3	ENST00000357798.9	TSL:1	c.2223C>T	p.Ser741Ser	synonymous	Exon 12 of 12	ENSP00000350446.5
	NPAS3	ENST00000548645.5	TSL:1	c.2172C>T	p.Ser724Ser	synonymous	Exon 11 of 11	ENSP00000448916.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1154718 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 558118

African (AFR) AF: 0.00 AC: 0 AN: 22834

American (AMR) AF: 0.00 AC: 0 AN: 8518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15222

East Asian (EAS) AF: 0.00 AC: 0 AN: 25852

South Asian (SAS) AF: 0.00 AC: 0 AN: 34788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3128

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 967976

Other (OTH) AF: 0.00 AC: 0 AN: 46670

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.96
PhyloP100		1.6

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: rs10142034; hg19: chr14-34269775;