19-55014200-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001083899.2(GP6):c.1745G>T(p.Ser582Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000239 in 586,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001083899.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000257 AC: 4AN: 155534Hom.: 0 AF XY: 0.0000236 AC XY: 2AN XY: 84676
GnomAD4 exome AF: 0.0000239 AC: 14AN: 586018Hom.: 0 Cov.: 6 AF XY: 0.0000221 AC XY: 7AN XY: 317018
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
GP6-related disorder Uncertain:1
The GP6 c.1745G>T variant is predicted to result in the amino acid substitution p.Ser582Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
not provided Uncertain:1
This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 582 of the GP6 protein (p.Ser582Ile). This variant is present in population databases (rs372168591, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with GP6-related conditions. 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