chr9-137040963-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015392.4(NPDC1):c.407G>T(p.Arg136Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000324 in 1,544,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R136Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_015392.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPDC1 | ENST00000371601.5 | c.407G>T | p.Arg136Leu | missense_variant | Exon 4 of 9 | 1 | NM_015392.4 | ENSP00000360660.4 | ||
NPDC1 | ENST00000371600.7 | c.641G>T | p.Arg214Leu | missense_variant | Exon 3 of 8 | 1 | ENSP00000360659.3 | |||
NPDC1 | ENST00000488145.1 | n.551G>T | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152146Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000216 AC: 3AN: 1392042Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1AN XY: 686154
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74334
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.407G>T (p.R136L) alteration is located in exon 4 (coding exon 4) of the NPDC1 gene. This alteration results from a G to T substitution at nucleotide position 407, causing the arginine (R) at amino acid position 136 to be replaced by a leucine (L). 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