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. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.2262C>G	p.Ser754Ser	synonymous_variant	Exon 12 of 12	ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.2262C>G	p.Ser754Ser	synonymous_variant	Exon 12 of 12	1	NM_001164749.2	ENSP00000348460.4

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

GnomAD3 exomes AF: 0.120 AC: 930 AN: 7762 Hom.: 60 AF XY: 0.122 AC XY: 604 AN XY: 4970

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 SAS exome AF: 0.0858

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

Gnomad4 AFR exome AF: 0.0625

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.0904

Gnomad4 EAS exome AF: 0.0216

Gnomad4 SAS exome AF: 0.0768

Gnomad4 FIN exome AF: 0.0745

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.138

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

Gnomad4 AFR AF: 0.0704

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.0968

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.0802

Gnomad4 FIN AF: 0.0652

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.139

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.89

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

Other links and lift over

dbSNP: rs10142034; hg19: chr14-34269775; COSMIC: COSV60861167;