14-52778458-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_198066.4(GNPNAT1):c.408G>A(p.Leu136Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000562 in 1,601,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_198066.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GNPNAT1 | NM_198066.4 | c.408G>A | p.Leu136Leu | splice_region_variant, synonymous_variant | Exon 6 of 6 | ENST00000216410.8 | NP_932332.1 | |
GNPNAT1 | XM_005268012.4 | c.408G>A | p.Leu136Leu | splice_region_variant, synonymous_variant | Exon 7 of 7 | XP_005268069.1 | ||
GNPNAT1 | XM_006720238.4 | c.408G>A | p.Leu136Leu | splice_region_variant, synonymous_variant | Exon 6 of 6 | XP_006720301.1 | ||
GNPNAT1 | XM_047431705.1 | c.408G>A | p.Leu136Leu | splice_region_variant, synonymous_variant | Exon 7 of 7 | XP_047287661.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GNPNAT1 | ENST00000216410.8 | c.408G>A | p.Leu136Leu | splice_region_variant, synonymous_variant | Exon 6 of 6 | 1 | NM_198066.4 | ENSP00000216410.3 | ||
GNPNAT1 | ENST00000650397.1 | c.408G>A | p.Leu136Leu | splice_region_variant, synonymous_variant | Exon 6 of 7 | ENSP00000496934.1 | ||||
GNPNAT1 | ENST00000557604.1 | c.408G>A | p.Leu136Leu | splice_region_variant, synonymous_variant | Exon 7 of 7 | 3 | ENSP00000452032.1 | |||
GNPNAT1 | ENST00000554230.5 | c.195G>A | p.Leu65Leu | splice_region_variant, synonymous_variant | Exon 5 of 5 | 5 | ENSP00000452310.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151970Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 239056Hom.: 0 AF XY: 0.0000231 AC XY: 3AN XY: 129778
GnomAD4 exome AF: 0.00000552 AC: 8AN: 1449080Hom.: 0 Cov.: 28 AF XY: 0.00000693 AC XY: 5AN XY: 720998
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151970Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74234
ClinVar
Submissions by phenotype
not provided Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. This variant has not been reported in the literature in individuals affected with GNPNAT1-related conditions. This variant is present in population databases (rs778581062, gnomAD 0.002%). This sequence change affects codon 136 of the GNPNAT1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GNPNAT1 protein. It affects a nucleotide within the consensus splice site. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at