chr11-66422853-GG-TC

Variant names:

• chr11-66422853-GG-TC
• NM_178864.4:c.610_611delGGinsTC
• NPAS4 p.Gly204Ser

Variant summary

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

The NM_178864.4(NPAS4):​c.610_611delGGinsTC​(p.Gly204Ser) 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: NPAS4 NM_178864.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56
• Publications: 0 publications found

Genes affected

NPAS4 (HGNC:18983): (neuronal PAS domain protein 4) NXF is a member of the basic helix-loop-helix-PER (MIM 602260)-ARNT (MIM 126110)-SIM (see SIM2; MIM 600892) (bHLH-PAS) class of transcriptional regulators, which are involved in a wide range of physiologic and developmental events (Ooe et al., 2004 [PubMed 14701734]).[supplied by OMIM, Mar 2008]

NPAS4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178864.4. 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
	NPAS4	NM_178864.4	MANE Select	c.610_611delGGinsTC	p.Gly204Ser	missense	N/A	NP_849195.2	Q8IUM7-1
	NPAS4	NM_001318804.1		c.90_91delGGinsTC	p.Ala31Pro	missense	N/A	NP_001305733.1	Q8IUM7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS4	ENST00000311034.7	TSL:1 MANE Select	c.610_611delGGinsTC	p.Gly204Ser	missense	N/A	ENSP00000311196.2	Q8IUM7-1
	NPAS4	ENST00000525148.1	TSL:1	n.610_611delGGinsTC		non_coding_transcript_exon	Exon 4 of 7	ENSP00000433135.1	Q8IUM7-3
	NPAS4	ENST00000524617.1	TSL:3	n.-31_-30delGGinsTC		upstream_gene	N/A

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		4.6

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: chr11-66190324;