chr19-45179382-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_212550.5(BLOC1S3):c.86G>C(p.Arg29Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000443 in 1,581,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. R29H) has been classified as Uncertain significance.
Frequency
Consequence
NM_212550.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLOC1S3 | NM_212550.5 | c.86G>C | p.Arg29Pro | missense_variant | 2/2 | ENST00000433642.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLOC1S3 | ENST00000433642.3 | c.86G>C | p.Arg29Pro | missense_variant | 2/2 | 2 | NM_212550.5 | P1 | |
BLOC1S3 | ENST00000587722.1 | c.86G>C | p.Arg29Pro | missense_variant | 1/1 | P1 | |||
MARK4 | ENST00000587566.5 | c.-276-79607G>C | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000430 AC: 9AN: 209362Hom.: 0 AF XY: 0.0000517 AC XY: 6AN XY: 116062
GnomAD4 exome AF: 0.0000448 AC: 64AN: 1429006Hom.: 0 Cov.: 30 AF XY: 0.0000408 AC XY: 29AN XY: 710626
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74372
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces arginine with proline at codon 29 of the BLOC1S3 protein (p.Arg29Pro). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is present in population databases (rs370018943, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with BLOC1S3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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