NM_013276.4:c.1338G>T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_013276.4(SHPK):c.1338G>T(p.Arg446Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_013276.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SHPK | NM_013276.4 | c.1338G>T | p.Arg446Ser | missense_variant | Exon 7 of 7 | ENST00000225519.5 | NP_037408.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SHPK | ENST00000225519.5 | c.1338G>T | p.Arg446Ser | missense_variant | Exon 7 of 7 | 1 | NM_013276.4 | ENSP00000225519.3 | ||
ENSG00000262304 | ENST00000572919.1 | n.1338G>T | non_coding_transcript_exon_variant | Exon 7 of 14 | 5 | ENSP00000461416.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250912Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135634
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461758Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727168
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 446 of the SHPK protein (p.Arg446Ser). This variant is present in population databases (rs759987504, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SHPK-related conditions. ClinVar contains an entry for this variant (Variation ID: 1435117). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at