NM_001164749.2:c.2208C>A

Variant names:

• chr14-33800515-C-A
• rs10141940
• NM_001164749.2:c.2208C>A

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.2208C>A​(p.Thr736Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,261,776 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000016 (0 hom.)
• Consequence: NPAS3 NM_001164749.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 9 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=-0.47).
• BP7: Synonymous conserved (PhyloP=0.186 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.2208C>A	p.Thr736Thr	synonymous	Exon 12 of 12	NP_001158221.1
	NPAS3	NM_173159.3		c.2169C>A	p.Thr723Thr	synonymous	Exon 12 of 12	NP_775182.1
	NPAS3	NM_001394988.1		c.2163C>A	p.Thr721Thr	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.2208C>A	p.Thr736Thr	synonymous	Exon 12 of 12	ENSP00000348460.4
	NPAS3	ENST00000357798.9	TSL:1	c.2169C>A	p.Thr723Thr	synonymous	Exon 12 of 12	ENSP00000350446.5
	NPAS3	ENST00000548645.5	TSL:1	c.2118C>A	p.Thr706Thr	synonymous	Exon 11 of 11	ENSP00000448916.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1261776 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 620220

African (AFR) AF: 0.0000416 AC: 1 AN: 24066

American (AMR) AF: 0.00 AC: 0 AN: 12418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19928

East Asian (EAS) AF: 0.0000368 AC: 1 AN: 27210

South Asian (SAS) AF: 0.00 AC: 0 AN: 60246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3606

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1023356

Other (OTH) AF: 0.00 AC: 0 AN: 51684

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	1.4
DANN	Benign	0.72
PhyloP100		0.19

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: rs10141940; hg19: chr14-34269721;