7-65960966-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000181.4(GUSB):āc.1887T>Gā(p.Ile629Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000181.4 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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GUSB | NM_000181.4 | c.1887T>G | p.Ile629Met | missense_variant | 12/12 | ENST00000304895.9 | NP_000172.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GUSB | ENST00000304895.9 | c.1887T>G | p.Ile629Met | missense_variant | 12/12 | 1 | NM_000181.4 | ENSP00000302728.4 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151858Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251490Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135920
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461792Hom.: 0 Cov.: 37 AF XY: 0.00000825 AC XY: 6AN XY: 727202
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151858Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74166
ClinVar
Submissions by phenotype
Mucopolysaccharidosis type 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 03, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 629 of the GUSB protein (p.Ile629Met). This variant is present in population databases (rs756035101, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with GUSB-related conditions. ClinVar contains an entry for this variant (Variation ID: 1051643). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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