rs10142034

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-33800569-C-G
• chr14-33800569-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001164749.2(NPAS3):​c.2262C>G​(p.Ser754Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,304,742 control chromosomes in the GnomAD database, including 16,434 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 0.12 (1372 hom., cov: 32)
  • Exomes 𝑓: 0.16 (15062 hom.)
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=1.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 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.2262C>G	p.Ser754Ser	synonymous	Exon 12 of 12	NP_001158221.1
	NPAS3	NM_173159.3		c.2223C>G	p.Ser741Ser	synonymous	Exon 12 of 12	NP_775182.1
	NPAS3	NM_001394988.1		c.2217C>G	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>G	p.Ser754Ser	synonymous	Exon 12 of 12	ENSP00000348460.4
	NPAS3	ENST00000357798.9	TSL:1	c.2223C>G	p.Ser741Ser	synonymous	Exon 12 of 12	ENSP00000350446.5
	NPAS3	ENST00000548645.5	TSL:1	c.2172C>G	p.Ser724Ser	synonymous	Exon 11 of 11	ENSP00000448916.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18713 AN: 150960 Hom.: 1372 Cov.: 32

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.0962

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.138

GnomAD2 exomes AF: 0.120 AC: 930 AN: 7762 AF XY: 0.122

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0649

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.156 AC: 180199 AN: 1153674 Hom.: 15062 Cov.: 34 AF XY: 0.155 AC XY: 86491 AN XY: 557542

African (AFR) AF: 0.0625 AC: 1427 AN: 22814

American (AMR) AF: 0.165 AC: 1401 AN: 8494

Ashkenazi Jewish (ASJ) AF: 0.0904 AC: 1374 AN: 15192

East Asian (EAS) AF: 0.0216 AC: 557 AN: 25840

South Asian (SAS) AF: 0.0768 AC: 2668 AN: 34726

European-Finnish (FIN) AF: 0.0745 AC: 2211 AN: 29688

Middle Eastern (MID) AF: 0.108 AC: 339 AN: 3126

European-Non Finnish (NFE) AF: 0.169 AC: 163814 AN: 967198

Other (OTH) AF: 0.138 AC: 6408 AN: 46596

GnomAD4 genome AF: 0.124 AC: 18726 AN: 151068 Hom.: 1372 Cov.: 32 AF XY: 0.119 AC XY: 8795 AN XY: 73844

African (AFR) AF: 0.0704 AC: 2912 AN: 41390

American (AMR) AF: 0.165 AC: 2506 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 335 AN: 3460

East Asian (EAS) AF: 0.0102 AC: 52 AN: 5102

South Asian (SAS) AF: 0.0802 AC: 387 AN: 4828

European-Finnish (FIN) AF: 0.0652 AC: 663 AN: 10170

Middle Eastern (MID) AF: 0.100 AC: 29 AN: 290

European-Non Finnish (NFE) AF: 0.167 AC: 11317 AN: 67650

Other (OTH) AF: 0.139 AC: 292 AN: 2100

Alfa AF: 0.0806 Hom.: 105

Bravo AF: 0.129

Asia WGS AF: 0.0500 AC: 162 AN: 3272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.89
PhyloP100		1.6
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: rs10142034; hg19: chr14-34269775; COSMIC: COSV60861167;