19-47039518-GTC-ATT

Variant names:

• chr19-47039518-GTC-ATT
• NM_002517.4:c.916_918delGTCinsATT
• NPAS1 p.Val306Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002517.4(NPAS1):​c.916_918delGTCinsATT​(p.Val306Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPAS1 NM_002517.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.47
• Publications: 0 publications found

Genes affected

NPAS1 (HGNC:7894): (neuronal PAS domain protein 1) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors. Studies of a related mouse gene suggest that it functions in neurons. The exact function of this gene is unclear, but it may play protective or modulatory roles during late embryogenesis and postnatal development. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002517.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS1	NM_002517.4	MANE Select	c.916_918delGTCinsATT	p.Val306Ile	missense	N/A	NP_002508.2
	NPAS1	NM_001321086.2		c.388_390delGTCinsATT	p.Val130Ile	missense	N/A	NP_001308015.1	Q99742-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS1	ENST00000602212.6	TSL:1 MANE Select	c.916_918delGTCinsATT	p.Val306Ile	missense	N/A	ENSP00000469142.1	Q99742-1
	NPAS1	ENST00000449844.6	TSL:1	c.916_918delGTCinsATT	p.Val306Ile	missense	N/A	ENSP00000405290.1	Q99742-1
	NPAS1	ENST00000906441.1		c.916_918delGTCinsATT	p.Val306Ile	missense	N/A	ENSP00000576500.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-47542776;