11-66423199-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_178864.4(NPAS4):c.775C>G(p.Leu259Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,609,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_178864.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPAS4 | ENST00000311034.7 | c.775C>G | p.Leu259Val | missense_variant | Exon 5 of 8 | 1 | NM_178864.4 | ENSP00000311196.2 | ||
NPAS4 | ENST00000525148.1 | n.698+258C>G | intron_variant | Intron 4 of 6 | 1 | ENSP00000433135.1 | ||||
NPAS4 | ENST00000524617.1 | n.58+258C>G | intron_variant | Intron 1 of 1 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152218Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457476Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 724510
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74374
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.775C>G (p.L259V) alteration is located in exon 5 (coding exon 5) of the NPAS4 gene. This alteration results from a C to G substitution at nucleotide position 775, causing the leucine (L) at amino acid position 259 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at