20-58694462-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_024663.4(NPEPL1):c.377C>T(p.Ala126Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_024663.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NPEPL1 | NM_024663.4 | c.377C>T | p.Ala126Val | missense_variant | Exon 3 of 12 | ENST00000356091.11 | NP_078939.3 | |
NPEPL1 | NM_001204872.2 | c.293C>T | p.Ala98Val | missense_variant | Exon 4 of 13 | NP_001191801.1 | ||
NPEPL1 | NM_001204873.2 | c.233C>T | p.Ala78Val | missense_variant | Exon 4 of 13 | NP_001191802.1 | ||
STX16-NPEPL1 | NR_037945.1 | n.2263C>T | non_coding_transcript_exon_variant | Exon 13 of 23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPEPL1 | ENST00000356091.11 | c.377C>T | p.Ala126Val | missense_variant | Exon 3 of 12 | 1 | NM_024663.4 | ENSP00000348395.6 | ||
STX16-NPEPL1 | ENST00000530122.1 | n.*360C>T | non_coding_transcript_exon_variant | Exon 13 of 23 | 5 | ENSP00000457522.1 | ||||
STX16-NPEPL1 | ENST00000530122.1 | n.*360C>T | 3_prime_UTR_variant | Exon 13 of 23 | 5 | ENSP00000457522.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248342Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134714
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461158Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726868
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74380
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.377C>T (p.A126V) alteration is located in exon 3 (coding exon 3) of the NPEPL1 gene. This alteration results from a C to T substitution at nucleotide position 377, causing the alanine (A) at amino acid position 126 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